Orthomolecular Tests - DNA genetic testing

 

 

Genetic Testing: What You Should Know to live better

 

What are genes and how are they related to disease?

Genes are segments of DNA. Genes are found in chromosomes and they control growth and help you stay healthy. Sometimes, when genes are abnormal or damaged, they may not work properly, which may lead to disease. Some genetic abnormalities, or “gene mutations,” may run in families. Some just happen by chance. Sometimes one mutation can cause a person to have a disease, but most diseases are caused by a combination of genetic and environmental factors.

 

What is genetic testing?

Genetic testing may help to show if you’ve inherited a tendency to get certain diseases. A sample of blood or skin is usually needed for genetic testing. Testing for gene mutations is gradually becoming available.

 

What does a positive test result mean? 

A positive test result means that you have the mutation you’ve been tested for. If you have a positive test result, it means you may be more likely to get a particular disease than most people, but it doesn’t mean you will definitely get the disease.

 

What does a negative test result mean? 

A negative test result means that you don’t have that particular mutation. This may mean that the disease doesn’t run in your family. A negative result doesn’t mean you won’t get the disease. It only means that you’re not more likely to get the disease than other people are.

 

Who should be tested?

By looking at your family history, your doctor can tell if you’re likely to have a gene mutation that may contribute to disease. A disease might run in your family if a blood relative developed the disease at a young age, if several family members have the disease or if the condition is rare. People from certain ethnic groups may also be more likely to get certain diseases. If one of your family members already has the disease, that person should be tested first. This helps show which genes, if any, are associated with the disease.

 

How do I decide if I should get tested?

If you think you may be at high risk for an inherited disease, talk to your family doctor. Your doctor will ask you questions about your health and the health of your blood relatives. This information will help your doctor find out what your risks might be. The information your doctor gives you about your risks can help you decide whether you want to be tested.

 

There are two important questions you should think about before you go through genetic testing:

 

1. What can I gain by being tested?

Here are some reasons you might want genetic testing:

 

2. Are there any negative effects of testing?

Here are some reasons you might not want to know that you could be at risk for a certain disease:


 

 

The Genetic test


The test is based on the analysis of 50 genetic polimorfismi, localizes to you on 36 geniuses, that they exercise an important role in the detossificazione processes, in the inflammatory process, the anti-oxidant activity, the sensibility to the insulin, the state of health of the heart and boneses.

 

You deepen the argument with the prof. Panfili and reserve one seen specialistica.

 

 

Directory of the geniuses investigates to you and of studied genetic varying:

 

Analyzed gene

Varying genetic studied

Role of the gene in the insorgence of cardiovascular pathologies

APOA1

-75 G>A

METABOLISM OF LIPIDS

Apo B

R3500Q

APOC3

C3175G

T3206G

APO AND

Cys112Arg

Arg158Cys

CETP

G279A

G1533A

GJA4 (CX37)

Pro319Ser

HMGCR

-911 C-A

LPL

C1595G

MMP3

-1171 5A>6A

NOS3

-786 T>C

Glu298Asp

VNTR introne 4

PON1

Gln192Arg

SREBF2

Gly595Ala

ADRA2B

Ins>Di Codon 299

METABOLISM AND OBESITY'

ADRB1

Gly389Arg

ADRB2

Gly16Arg

Gln27Glu

ADRB3

Trp64Arg

NPY

Leu7Pro

PPARG

Pro12Ala

CBS

C699T

Metabolism of the Omocisteina

T1080C

MTHFR

C677T

A1298C

MTR

A2756G

MTRR

A66G

ACT

-51 G-T

Inflammatory answer

IL-1B

-511 C-T

IL-6

G-634C

G-174C

IL-10

G-1082°

TNFα

-308 G-A

MnSOD

C (- 28) T

Anti-oxidant activity and DETOSSIFICAZIONE

T175C

SOD3

C760G

GSTP1

I105V

A114V

GSTM1

delezione of the gene

GSTT1

delezione of the gene

VDR

Fok1 (ATG ®ACG codon 1)

bony metabolism and osteoporosis

BsmI (ACTS introne 8)

TaqI (T-C esone 9)

COLIA1

Intr. 1 2046 G-T

CTR

Pro463Leu

ESR1

PvuII (IVS1-397 T/C)

XbaI (IVS1-351 A/G)


 

THE NUTRIGENETIC

The more recent discoveries on the human genome supply us the instruments and the bases in order to comprise the molecular mechanisms through which single geniuses, or they combinations, answer to the changes in the diet and the style of life (exposure to the cigarette smoke, alcohol consumption etc), rendering one individual particularly sensitive to contract a sure type of pathology and to make light on the mechanisms through which the diet, influencing the genic expression, can exercise a protecting effect. After all the potentialities offered from this new approach introduce to us in one new were of science of the nutrition, the nutrigenetica.


The nutrigenetica regards the identification of the genetic variations in the man that cause differences in the fenotipica answer to molecules introduced with the diet, the objective to estimate the risks and the benefits for the individual of determined members of the diet. In practical terms us, with the nutrigenetica it is possible to develop to a nutrition personalized to the genetic constitution of the individual, holding account of the variability of the geniuses been involved in the metabolism of the nourishing and its target.
The nutrigenetica can be taken advantage of powerful instruments in a position to supplying specific information, characterizes them and premature, regarding the traditional diagnostic systems, on the role estimate carried out from the nourishing. They have been put to point technical bio-molecular in order to characterize the geniuses and to clear the interactions between these and the nourishing.


The conceptual bases of this new branch can be reassumed in the following points:

 

PREVENTIVE MEDICINE

The plan human genome has delivered international to the scientific community a genetic sequence of three billions of seems of bases shared to 99.9% from all the individuals. The differences between individuals are constituted for the greater part from nucleotidici polimorfismi, that is changes of one single base in the DNA.
In medical field, the new acquaintances on the Human Genome have allowed consolidating of one new molecular dimension of the medicine, in particular of a field defined like “Predittiva Medicine”, that is a medicine, than being based on the ricavabili information from the genetic constitution of an individual, can anticipate an esteem of the risk of this last one to develop one determined pathology during the course of the life.
The interest for the genetic member of the susceptibility to complex diseases is assuming more and more importance in the modern medicine, in how much the role of some relatively common genetic polimorfismi is being put in evidence, but that if associates to you between they and arranges to you with component detailed lists acclimatizes them, they can remarkablly elevate the risk to develop diffuse pathologies in the industrial society.
 

THE PERSONALIZED NUTRITION

With the nutrigenetica, “the personalized” medicine concept comes extended to the area of the nutrition. If you want to deepen yours genetic member they exist of the tests aimed you that they can foirniurvi precious and only (yours) keys of reading in order to comprise if ilo your body to the stregua of a motor vehicle must be resupplied with combustile, to benzine, gasolo or GPL…. The genetic variability characterizes them comparativily places to us to consider the organism like a puzzle unsolved, of which they are being begun to decipher the programs of I use codifies to you in the same geniuses that as hard disk they contain myriads of indformazioni that are necessary to know for being able to guarantee a perfect operativity, determining as the nourishing they come it assimilates to you, metabolizzati, it accumulates to you and in end it excretes, it is to the base of the peculiarity of everyone in answering to molecules introduced in the organism and, in general terms, to the alimentary styles and of life. (for info on tests delo the well-being: www.aimo.it)
Without a doubt but the more fascinating of the opportunities that they are opened in the field of the nutrigenetica is the development, leaving from the genetic differences characterizes them, of a “personalized nutrition”, in order to obtain one effective “healthy” dietetic therapy in a position to preventing or delaying the insorgence of pathologies correlated to the feeding, for single individuals or particular subgroups.


INTERACTION GENE-DIET

The concept that the acquaintances on the nutrizionali demands, the state of nutrition and the genotype of an individual or a subgroup of population can be used for the prevention and the cure of some pathologies turns out of easy and immediate understanding as far as situations like the nutrizionali deficiencies, but sure less obvious for a group of approximately 50 human genetic diseases caused from the presence of varying in geniuses that they codify for enzymes been involved in specific metabolic ways. Everyone of our geniuses possesses approximately 10 differences in its “code” regarding the “gene standard”, these shunting lines come calls “polimorfismi” (SNPs= single gene polymorphisms) and varying that of they achieve “alleli”. It is obvious that, seen relative vhf with which such mutations they resort in the genome, all the polimorfismi do not cause serious implications for the health, the greater part of they instead exhibits only an light effect on the functionality of the protein for which it codifies. The differences characterize them that of they turn out can explain because all we do not react in identical way to the several sollicitations and the nutrigenomica exactly describes the changes in the genic expression as a result of a specific nutrizionale participation. The molecules that we introduce with the diet can modulate specific aspects of the cellular physiology, acting from ligandi for the receivers of the transcription factors, altering the substrate concentrations and metaboliti and, through interactions to level of nucleici acids, influencing specific ways of translation of it marks them.

 

METABOLISM OF LIPIDS

The graasi or lipids are more study you determining of the cardiovascular diseases and the understanding of the molecular mechanisms to the base of the disorders of the lipidico metabolism is of great importance for the prevention of the cardiovascular diseases.
The geniuses been involved in the regulation of the lipidico metabolism up to now identify to you are most numerous and the directory is not still complete. Moreover it is famous that the steady state of the lipidico metabolism is regulated also from various factors acclimatizes them not genetic like habit to the smoke of cigarette, alcool consumption, composition of the diet and physical activity.
Although to the state they of the acquaintances puts into effect is not possible to establish with precision the contribution of the genetic factors and of the factors she acclimatizes them in the etiologia of the dislipidemie, however they are the many rare cases in which a dislipidemia manifest for effect of a genetic alteration in absence of a context gets used predisposing they, and also in these cases the factors acclimatize them are however in a position to modulating the severità of the metabolic disorder and to influence the age in which this manifest.

Under the profile of the public health the nutrition is the factor acclimatizes them more important that the appearance of disorders of the lipidico metabolism interacts with our geniuses in modulating. It is famous that the concentration of lipids put molding on to us is a lot influenced from the content of fat people saturates of the diet and that to level of population the medium cholesterol concentrations more are elevated in those countries that consume rich diets of fat people saturate and more lowlands in the countries with poor diets of rich fat people and of vegetables and fibers. However to level of the individual the variation of lipids put molding on to us in answer to dietetic modifications is variable, some subjects answers very well, while others are relatively insensitive. In some cases, high levels of cholesterol have been observe to you in correlation to specific genic mutations and the persons who carry such mutations represent subjects to high risk of cardiovascular pathologies.

 

Apolipoproteina A1 (APOA1): polimorfismo -75 G>A

The apolipoproteina A1 (APOA1) constitutes the greater proteico member of ipoproteins to high density (HDL, the so-called good cholesterol). Since APOA1 exercises an important role in the inverse transport of the cholesterol, bottoms sierici levels of APOA1/HDL represents very known factor of risk of pathologies of coronariche arteries (CAD). A frequent polimorfismo of gene APOA1 localizzatio in the promotore region, -75G>A, modulates the expression of the apolipoproteina A1. Important interactions between this polimorfismo, dietetic habits and levels of HDL very are known. The bearers of allelica varying of the polimorfismo -75G>A, can increase to their sierico level of HDL in answer to one greater assumption with the fat acid diet insaturi. Jeenah (1990) Mol Biol Med 7, 233
Apolipoproteina B (Apo B): mutation R3500Q
The apolipoproteine are of proteins pertaining to the complexes VLDL and LDL (Very Low Density Lipoproteins and Low Density Lipoproteins) and are responsible of the solubility of lipids in the blood and their resorption in the cells. In particular, the apolipoproteina B-100 (Apo B-100) is necessary for the solubility and the resorption of the cholesterol. The Apo complex B-100-cholesterol comes recognized from the riassorbito membrane receivers LDL and therefore in the cells. The gene that codifies the Apo B-100 is subject to polimorfismi of which, the most frequent (R3500Q), provokes one lessening of the affinity of the tie Apo B-100- “receiving LDL of membrane”. The Apo changed B-100 remains free in the blood, causing ipercolesterolemia and an increase of the risk of formation of ostruttive plates. Moreover the mutation of this protein is an important factor of risk for the development of the premature arteriosclerosis and the arterial coronariche deficiencies (coronary artery disease, CAD). It has been demonstrated that the 3,5% of the cases of ipercolesterolemia mutation has like primary cause one on the gene of the Apo B-100. This type of mutation is known clinical also like Familial Defective apolipoprotein B-100 (FDB). Studies on patients with FDB have demonstrated that their level of cholesterol is medium of 8 mmol/l, while the normal value is smaller of 5.2 mmol/l.
The mutation of this gene, than is found on chromosome 2, provokes in the protein one substitution of the amino acid Arginina with one Glutamina in position 3500 (R3500Q); this exchange between amino acids has like consequence a change of the conformation of the terziaria structure of the Apo B-100, in the zone of acknowledgment for the receiver LDL. The lessening of affinity between Apo B-100 and receiver LDL can be advanced to 20% in the patients omozigoti. The prevalence of this mutation in the varied caucasica population from 1:700 to 1:500. Soria (1989) Proc Natl Acad Ski U S To 86, 587
Apolipoproteina C3 (APOC3): polimorfismi C3175G and T3206G
The Apolipoproteina C3 (APOC3) exercises an important role in the metabolism of lipids, inhibiting the metabolism of triacil-glicerolo to work of the enzyme the ipoprotein-lipasi, with consequent increment of the level of trigliceridi (ipertrigliceridemia). Polimorfismi C3175G and T3206G of gene APOC3 are associate you to a advanced risk 4 times of ipertrigliceridemia and to an elevated risk of insorgence of infarcts, cardiovascular arteriosclerosis and pathologies. (Newman (2004) Eur J Hum Genet 12, 584; Xu CF ET to (the 1994) Clin Genet. 46:385 - 97).

 

Apolipoproteina and (APO and): genotipizzazione alleli E2, E3, E4

Gene APOE, is situated on chromosome 19 and codifies for apolipoproteina and (APOE), one plasmatica protein, been involved in the transport of the cholesterol, than alloy to the amyloid protein. Three are present isoforme (various structural conformations of the same protein) of ApoE: Apoε2, Apoε3 and Apoε4, that they modulate the impact of the diet on the concentration of lipids put molding on to us. Such isoforme is the products of 3 various alleliche shapes (ε2, ε3, ε4), determined from the change of amino acid in two various positions (varying Cys112Arg and Arg158Cys).
The apolipoproteine carry out a fundamental role in the catabolism of rich ipoproteins of trigliceridi and cholesterol. The APOE comes synthetized mainly in the liver and has the function of lipidico conveyor. And' famous for a long time that it elevates to you levels of cholesterol constitute one of the greater factors of risk for the cardiovascular diseases. In particular not only the level of cholesterol total but also the relative levels you of HDL, LDL and trigliceridi cover remarkable importance in the pathogeneses of the vascular diseases. The APOE has been one of the first genetic markers to being studies to you like factor of risk for the infarct of the myocardium. Studies carry out on one wide population to you of patients with infarct of the myocardium and relative control group has confirmed given already present in literature where the allele ε4 of APOE (APOE4) it had been considered a factor of genetic risk for the cardiovascular diseases. The bearers of allele the 4 introduce in fact levels more elevate you than cholesterol total and LDL, in presence of a rich feeding in cholesterol, and therefore has a greater risk to develop cardiovascular pathologies. However these subjects are also those that answer better when subordinates to diets with reduced contained of fat people, while the varying bearers of ApoE2 and 3 introduce variable answers. Weisgraber, 1981, J. Biol. Chem. 256:9077 - 9083; Rall, 1982, Proc. Nat. Acad. Ski. 79:4696 - 4700; Das, 1985, J. Biol. Chem. 260:6240 - 6247; Paik, 1985, Proc. Nat. Acad. Ski. 82:3445 - 3449.

 

Cholesterol ester transfer protein (CETP): polimorfismi G279A and G1533A

The CETP is been involved in the metabolism of lipids, having mediated the lipid exchange between ipoproteins by means of the transfer of foreign countries of the cholesterol from the HDL to rich ipoproteins of trigliceridi, with consequent reduction of the levels of HDL. The polimorfismo of introne the 1 of gene CETP G279A increases the concentrations of the CETP and reduces the levels of HDL in favor of LDL and VLDL. An other polimorfismo, G1533A, localized in esone the 15 of gene CETP, that it determines the aminoacidica variation Arg->Gln to level of codone the 451, are anch' associated it to one increased activities put molding on us of the CETP. Reduced levels of HDL they are associates you to an increased risk of cardiovascular pathologies. Freeman ET to (1990), Clin Ski. ; 79: 575-581; Kakko ET to (the 1998) Atherosclerosis. 136 (2): 233-40

 

GAP JUNCTION PROTEIN ALPHA 4 (CONNESSINA 37): varying Pro319Ser

The Connesina 37 (CX37) constitutes an important been involved molecular factor in the development of goes arteriosclerotics. The CX37 is expressed in the endoteliali cells and is codified from gene GJA4. Aminoacidica varying to level of codone the 319 (Pro319Ser) of such gene constitutes a marker prognosticates for the development of plates arteriosclerotics and a marker of genetic risk for the arteriosclerosis. Boerma (1999) J Med Interior. Aug; 246 (2): 211-8.

 

Idrossi-metil-glutaril-coenzyme To reduttasi (HMGCR): polimorfismo -911 C-A

The idrossi-metil-glutaril-coenzyme To reduttasi (HMGCR) is a gene that it codifies for omonima the protein. This is a fundamental enzyme for the synthesis of the cholesterol. Already it has been remembered previously that it elevates levels to you of cholesterol are a factor of risk for the cardiovascular diseases, since predispose to the formation of the aterosclerotiche lesions. It is interesting to notice that given its strategic position in the biosintetica chain that door to the cholesterol synthesis, the HMGCR is also the target farmacologico of the statine, a drug family that acts lowering the levels of cholesterol. This effect comes obtained inhibiting the carried out enzymatic action from the HMGCR. On the base of these observations it has been studied a polimorfismo in the promotrice region of gene HMGCR in position -911 that consists in substitution of one C (citosina) with one To (adenina). This polimorfismo has been studied in one wide coorte of patients with infarct of the myocardium and relative control group. The polimorfismo has turned out to be associated to an increased risk to develop the infarct of the myocardium. In particular the presence of To in the polimorfismo of the HMGCR turned out associated to the infarct in juvenile age. Licastro Neurobiol Aging. 2006

 

Ipoprotein lipasi (LPL): polimorfismo C1595G

The ipoprotein lipasi (LPL) is an enzyme been involved in the metabolism of the trigliceridi in circulating ipoproteins. This enzyme is synthetized from the cells of the adiposo and muscular woven one and after to be secreto it is transported on the endothelium of the capillaries, where it interacts with rich ipoproteins in trigliceridi. The LPL improves the absorption of ipoproteins from part of the liver and of the walls of it is gone blood.
Polimorfismo C1595G seems to have a beneficial role in how much has been associated with a diminished risk of insorgence of cardiovascular pathologies, reduced arterial pressure and bottoms levels of trigliceridi. (Kobayashi ET to, 1992 Biochem Biophys Res Commun. 15; 182: 70-7)

 

Metalloproteinasi of matrix 3 (MMP3): promotore polimorfismo -1171 5A>6A

The metalloproteinasi are one important enzyme family in the process of rimodellamento of the extracellular matrix and in the age-employee hardening of the arteries, and therefore been involved in the aterosclerotica aetiology and in particular in the evolution of the plates.
The aterosclerotiche plates are constituted from two main members: woven rich of lipids and one sclerotico rich of collagene. The sclerotiche plates are from considering themselves less to risk in how much are stablest; on the contrary the ateromatosa member “motivatings force” gives instability to the plate and she more renders it more friabile and therefore to risk of trombotici events. In these mechanisms it has been wide demonstrated the role of the Metalloproteinasi, in how many enzymes deputies to the reorganization of the same plates.
Recently, in the zone of the promotore (in position -1171) of gene MMP3, a member of the family of the MMP, it has been characterized a polimorfismo (5A>6A) that it influences the enzymatic activity of MMP3. The allele 5A it determines a greater activity and it has been associated with a greater risk of infarct to the myocardium, while the allele 6A it determines a reduced activity of the enzyme and constitutes a marker of risk for the arterial stenosis. For this polimorfimo, the experts suggest that the optimal genotype is one eterozigoti for the alleli (5A/6A). Ye (1996) J Biol Chem271 (22): 13055-60

 

Oxide endoteliale sintetasi (eNOS): polimorfismi -786 T>C, Glu298Asp and VNTR introne 4

In the vascular system, the nitric oxide () does not exercise an important role producing to vasodilatation, regulating the blood flow and the arterial pressure, and conferring protecting tromboresistenza and property to the endothelium of it is gone blood. The endothelium-employee vasodilatation is mediated from the release not produced from oxide endoteliale sintetasi (eNOS). A reduced synthesis or in its smaller bioavailability could not be the cause of the reduced endothelium-employee vasodilatation that it is observed in is gone blood of subject cardiovascular factors of risk, which smokers assets and liabilities to you, patients with hypertension or ipercolesterolemia. The lack of Not-mediated effects can moreover predispose to the development of arteriosclerosis.
The polimorfismo -786 T>C of the promotore region of the codifying gene oxide endoteliale sintetasi (NOS3) reduces the NOT endoteliale synthesis, suggesting that the bearers of such nucleotidica variation are predisposed to the insorgence of coronariche pathologies. But the indication more important is given from the fact that this reduction is esacerbata from the cigarette smoke.
Varying missense the Glu298Asp, present to level of esone the 7 of gene NOS3, would act in synergy with the polimorfismo of the promotore region, increasing the risk of coronariche pathologies ulteriorly.
A rare polimorfismo VNTR localized to level of introne the 4 of gene NOS3 (Ins>Di Introne 4) represents a factor of risk of infarct to the myocardium (ME). The frequency of this varying has been shown meaningfully more elevated (than approximately 7 times) in patients with ME without known secondary factors of risk. This varying has been moreover associated with arterial stenosis, especially in combination with the traditional factor of risk of the cigarette smoke. Yoshimura (1998) Hum Genet 103, 65; Nakayama (1999) Circulation 99, 2864; Wang (1996) Nat Med; 2: 41-45.
 

PARAOXONASI 1 (PON1): polimorfismo Gln192Arg

The Paraoxonasi is an soccer-employee glycoprotein, that it circulates in ipoproteins to high density (HDL), in a position to preventing the perossidazione of ipoproteins to low density (LDL) and to contrast therefore the ateromasico process. Gene PON1, codifying such protein, belongs to a multigenic family with to others two PON-similar geniuses, calls PON2 to you and PON3, all localizes to you on the long arm of chromosome 7. Various polimorfismi of the cluster are famous of geniuses PON: the polimorfismo Gln192Arg in gene PON1; it has been associated to cardiovascular risk, in how much favoring the aterosclerotico process. Ranade (2005) Stroke. 36 (11): 2346-50.

 

STEROL REGULATORY ELEMENT BINDING TRANSCRIPTION FACTOR 2 (SREBF2): polimorfismo Gly595Ala

The family of the SREBP has an important role in the regulation of the cellular metabolism of the cholesterol and fat acids. A member of this family, the SREBF2, exercises a role key in the steady state of the cholesterol, activating the mediated cholesterol absorption put molding on to us from the receiver of LDL. A polimorfismo SNP of the gene SREBF2, Gly595Ala, than cause a aminoacidica variation Gly>Ala to level of codone the 595, is associated to ipercolesterolemia. Durst (2006) Atherosclerosis. Dec; 189 (2): 443-50.
 

METABOLISM AND OBESITY'

The obesity is a complex disease due to genetic factors, it acclimatizes them and it characterizes them with consequent alteration of the energetic budget and I accumulate excessive of woven adiposo in the organism. Studies on families have always supported the hypothesis of a genetic infuence, in charge of the so-called metabolic anomalies that would facilitate the insorgence of the obesity in presence of high availability of alimony and chronic sedentarismo. The obesity represents an important factor of risk for the insorgence of cardiovascular diseases.

 

Adrenergic receiver alpha 2B: Ins>Di mutation Codon 299

The adrenergic receivers alfa2 influence the energetic metabolism through the inhibition of the insulin secretion and the lipolisi. The gene Codon 299 codified for the adrenergic receiver Alfa2B (ADRA2B) introduces a polimorfismo Ins>Di. Varying Of Codon 299 is much common one in the caucasici (approximately 31%) and has been associated in alive with one reduced expansion of the brachiali arteries and with a reduced flow of the coronariche arteries. Moreover it is believed that such varying it affects the metabolism it bases them and it contributes to the obesity. Heinonen (1999) J Clin Endocrinol Metab. 84 (7): 2429-33
 

Adrenergic receiver Beta 1 (ADRB1): polimorfismo Gly389Arg

The adrenergic receivers beta 1 are the main receivers cardiaci for Nor-Epinefrina and Epinefrina, that they represent the more important mechanism by means of which the blood flow is increased to work of the likeable nervous system. Gene ADRB1, codifying for the adrenergic receiver B1. it introduces a polimorfismo, Gly389Arg, consisting in the aminoacidica variation Gly - Arg to level of codone the 389. The varying Arg389 is associated to one better recettoriale function. Such varying it seems to predispose to infarct and to influence bloccanti the therapeutic answer to the treatment with Beta. The varying Arg389 moreover is associated to hypertension. Mason 1999 J Biol Chem. Apr 30; 274 (18): 12670-4; Iwai C, Am Heart J. 2003 Jul; 146 (1): 106-9

 

Adrenergic receiver Beta 2 (ADRB2): polimorfismi Gly16Arg and Gln27Glu

Allele the Arg16 of gene ADRB2 determines an improvement of the sensibilizzazione of the receiver and has been associated to hypertension. The contemporary presence of varying the Arg16-Gln27 of the ADRB2 involves one reduced vasodilatation mediated from the adrenergic receiver Beta 2. The varying Glu27 is associated to an increment of the activity of the receiver, with consequent obesity and metabolic pathologies. Large 1997 J Clin Invest.100 (12): 3005-13.
 

Adrenergic receiver Beta 3 (ADRB3): polimorfismo Trp64Arg

On the base of its biological role in the metabolism of lipids, it is believed that the adrenergic receiver Beta 3 is one of the geniuses that it influences I accumulate it of the fat person in the body. A mutation missense to level of codone the 64 of gene ADRB3 has been associated with an increase of body mass index (the BMI). Kadowaki 1995 Biochem Biophys Res Commun. 215:555 - 60.
 

NEUROPEPTIDE Y: polimorfismo Leu7Pro

The Neuropeptide Y (NPY) exercises an important role in the regulation of the energetic balance, mediating the stimulation to the food assumption and I accumulate it energetic. Between the multiple actions of the NPY they come also ricompresse vasoconstriction, regulation of the blood pressure, metabolism of the cholesterol and pathogeneses of the arteriosclerosis.
A rare polimorfismo of the gene codifying for NPY, Leu7Pro, has been associated to elevated cholesterol amount total and LDL, especially in the patients with obesity. Such polimorfismo, moreover, is marker for the risk of hypertension and an arteriosclerosis. Karvonen 1998 Nat Med. Dec; 4 (12): 1434-7.

 

Receiver activated from the proliferatori of perossisomi - range (PPARG): polimorfismo Pro12Ala

PPAR-range (PPARG) is a receiver that well-known carries out an important role in the stimulation of the natural process of the body to the base of the regulation of the lipidico metabolism and carbohydrates, increasing the sensibility to the insulin. The elevated arterial pressure, the lipidiche anomalies, the resistance to the insulin and the obesity center them are the main members of the metabolic syndrome, than commonly prelude to cardiovascular pathology and the diabetes of type 2. The characteristic of the metabolic syndrome is that one to re-unite the greater factors of cardiovascular risk comprised the obesity centers them, the resistance to the insulin, the arterial pressure elevated and the anomalies of lipids in the blood. Nearly a quarter of the world-wide population is affection from metabolic syndrome. Until a maximum of 80% of nearly 200 million adults in the world hit from diabetes they pass away because of cardiovascular pathologies. The persons affette from metabolic syndrome are mainly to risk regarding the others in how much have the double quantity of the probabilities to die for cardiac attack and the triple one of the probabilities to die for ictus.
Some studies support a beneficial role of the polimorfismo Pro12Ala, that it is associated with one reduced transcription of the PPARgamma2 gene. Such polimorfismo, moreover, is associated with one lessening of body mass index (the BMI), reduction of the levels of insulin, increase of the levels of HDL and improved sensibility to the insulin. Therefore, the polimorfismo Pro12Ala diminishes the risk mellito diabetes of type II.

 

METABOLISM Of the OMOCISTEINA

During the last few years they are gone accumulateing always greater scientific evidences on as levels clinical increase you of omocisteina represent a new independent factor of cardiovascular risk that can be placed side by side to the other traditional factors of risk or that it can upgrade of the deleterious effects on the arterial wall. The cigarette smoke and the dietetic contribution of folati and B12 vitamin are between the main determinants of the plasmatiche concentrations of omocisteina. The omocisteina would seem to induce the vascular damage interfering with with the nitric acid production from part of the endothelium, determining hyperplasia of the smooth muscular cells and increasing to the production of free radicalses with consequent ossidativo damage and lipidica perossidazione (therefore favoring the formation of the aterosclerotica plate), let alone interfering with the piastrinica function and increasing the tendency to the thrombosis. The iperomocisteinemia it covers, moreover, important implications in the human reproduction connected at the concezionale moment (repeated abortions), to the gravidico state (vasculodipendenti pathologies which preeclampsia, defect of fetal increase, separation of placenta) and to the menopause.
Cistationina Beta Sintetasi (CBS): polimorfismi C699T and T1080C
The CBS is an enzyme necessary in order to convert the omocisteina in Cistatione. Such enzyme reduces the levels of omocisteina. And' demonstrated state that two polimorfismi of gene CBS (C699T and T1080C) determine an increase of the activity of the enzyme, reducing the amount of omocisteina in the blood. Such polimorfismi are associate to you with a reduced risk of insorgence of coronariche pathologies.

 

MTHFR (Metilentetraidrofolatoreduttasi): polimorfismi C677T and A1298C

Metilentetraidrofolatoreduttasi (MTHFR) is an enzyme been involved in the metiltetraidrofolato metilentetraidrofolato transformation of the 5-10 in 5 that it serves like methyl donor for the rimetilazione of the omocisteina to metionina through the participation of the B12 vitamin.

Rare mutations (transmitted with recessiva autosomica modality) can cause the serious deficiency of MTHFR with enzymatic activity inferior to 20% and appeared of omocisteinemia and omocistinuria and bottoms levels put molding on us of folic acid. The clinical symptomatology is serious with delay of the psychomotor development and massive trombotici phenomena.
Beside the serious deficiency of MTHFR it has been identified a common genetic polimorfismo, had to substitution of one C (citosina) in T (timina) nucleotide to the 677 (C677T), than cause one substitution of one alanina in valina in the final protein and one reduction of the enzymatic activity of the equal MTHFR to 50%, until 30% in conditions of exposure to the heat (varying termolabile). Such varying it involves levels elevates in the omocisteina blood species to you after oral cargo of metionina. This polimorfismo, however, does not have consequences on the levels of omocisteina if the content of folati of the diet is elevated, but it is associated to iperomocisteinemia if the folic acid content of the diet is insufficient. In the same way the subject bearers of varying 677CT are also those that answer better when subordinates to one supplementazione of the diet with folati.
The genic frequency in Europe of the mutation is of the 3-3,7% that involves one condition of eterozigosi in approximately the 42-46% of the population and of equal omozigosi to 12-13%. Recently, a second mutation of gene MTHFR (A1298C) has been associated to one reduced enzymatic activity (approximately 60% singularly; approximately present 40% if in combination to mutation C677T). This mutation, in patients bearers of mutation C677T, determines an increase of the levels emati us of omocisteina.
Perhaps levels increase you of omocisteina in the blood are today consider factor you of risk for vascular disease, (arterial thrombosis) through a mechanism mediated from the sulfidrilici groups on the endoteliale wall of are gone. Moreover in conditions of alimentary deficiency of folic acid varying termolabile of the MTHFR the door to levels many bottoms the folic acid in the plasma and is therefore a factor of risk for the defects of the neurale tube in the women in pregnancy. Frosst ET to (1995) the Natures Genet. 10:111 - 113; Van der Put ET to (the 1998) Am. J. Hum. Genet. 62:1044 - 1051.
 

Metionina sintetasi gene (MTR): polimorfismo A2756G

Gene MTR codifies for an enzyme that is been involved in the conversion of the omocisteina in metionina. Polimorfismo A2756G increases the activity of this enzyme, affecting the levels emati us of folato and omocisteina. Reduced levels of omocisteina they reduce the risk of insorgence of cardiovascular pathologies. Moreover, it has been demonstrated that the presence of polimorfismo A2756G determines one lessening of the probabilities of defects of the neurale tube during the pregnancy and a diminished risk of venosa thrombosis. Leclerc (1966) Hum. Molec. Genet. 5:1867 - 1874

 

Metionina sintetasi reduttasi (MS_MTRR): polimorfismo A66G

The Metionina sintetasi reduttasi is a necessary enzyme for the formation of deriving of the B12 vitamin. Such enzyme is indispensable in order to maintain an adequate amount of cellular B12 vitamin, metionina and folato, and in order to maintain to bottoms the levels of omocisteina. Polimorfismo A66G is associated with an increase of the risk of cardiovascular, independent diseases from the levels of omocisteina. And' state moreover demonstrated that such polimorfismo you increase the risk of defects of the neurale tube, bifid thorn and syndrome of Down during the pregnancy. Brown (2000) J Cardiovasc Risk 7, 197

 

INFLAMMATORY ANSWER

It is famous from many years that the deposition of fat derives to you from the cholesterol in the wall of is gone induces an activation of normally present cells in this zone of is gone calls to you macrofagi. The macrofago after ingestion of this material it comes activated and it induces an anomalous inflammatory answer in the wall of the vase that with the time door to the formation of the aterosclerotica plate and to the typical vasali alterations of the atherosclerosis. Therefore members and factors to regolatoria activity on the inflammatory answer play an important role in the development and the clinical manifestation of the complicanza of the atherosclerosis, which the infarct of the myocardium.

 

Interleuchina-1B (IL-1B): polimorfismo -511 C-T

The gene of interleuchina-1 (the IL-1) is situated on chromosome 2 where an aggregate of geniuses is present that it codifies is for the IL-1b, IL-1a that and for the receiver of these two molecules. The IL-1 is a pluripotente, that is able citochina to carry out and to regulate many of immunity functions and above all is been involved in the activation of the inflammatory answers. The IL-1b in particular comes also rilasciata in the circolatorio torrent exercising ance sets in action diffuse in the organism. In fact, it is one of the factors able to induce fever, sleep, anorexia and hypotension. This interleuchina is important in the pathogeneses of the infarct of the myocardium in how much stimulates macrofagi and endoteliali cells to rilasciare tissutale factor (TF), powerful inducer of the thrombi. The present polimorfismo on the promotore of the IL-1b in position -511 consists in substitution of one C (citosina) with one T (timina). The presence of allele T in concomitanza with determines to you alleli of other polimorfismi on other geniuses increases the risk to develop the disease, therefore the subject bearers of such genotype, soprattuto when present with to other genotypes, have greater probabilities of having the infarct of the myocardium regarding not the bearers. Instead, in the subjects with protecting polimorfismo IL-1 beta the coagulation of the blood comes in such a way induced in measure much minor, reducing the probabilita' of being exposed to the risk of infarct or ictus. Mattila (2002) J Med Genet 39, 400

 

Interleuchina-6 (IL-6): mutations G-634C and G-174C

The gene of interleuchina-6 (the IL-6) is situated on chromosome 7 and codifies for omonima the protein. The IL-6 is one pleiotropica citochina, in a position to carrying out many functions; generally it has for-inflammatory action, therefore it induces the inflammatory answers. The IL-6 is been involved in the regulation of the inflammatory answer is acute that chronic and in the modulation of the specific of immunity answers. It is by now famous that the inflammation has a main role in the pathogeneses of the atherosclerosis since the aterosclerotiche plates and the associate lesions introduce infiltrating of activated of immunity cells and one increased inflammatory molecule synthesis. On this subject the IL-6 has been one of the first citochine studied in the cardiovascular diseases in how much promotes the formation of the ateromi, dislipidemia and hypertension. Vary studies that have followed populations in the time have proposed to use the plasmatico level of this protein like predittivo marker of the infarct. In fact it has been observed that the levels emati us of the IL-6 increased much time before the clinical manifestation of the infarct and correlated with the incidence of the disease. The gene of the IL-6 contains varies polimorfismi between which one present in the promotore in position -174 that consists in the substitution of G (guanina) with one C (citosina), and an other present in position -634, also this characterized from the substitution of G with one C. From studies lead on a group of patients with infarct to the myocardium and on a group of healthy subjects without cardiovascular pathologies is emerged that these polimorfismi represent a factor of risk for the infarct. That is the bearers of the allele changed C have one greater probability of being hit from such pathology regarding not the bearers. Moreover the presence of these alleli correlates also with greater levels put molding on us of IL-6. Fishman (1998) J Clin Invest 102, 1369.

 
Interleuchina-10 (IL-10): mutation G-1082A

The interleuchina 10 (IL-10) is a gene situated on chromosome 1 and codifies for omonima the protein. It is an anti-inflammatory molecule that is it inhibits the release of the for-inflammatory citochine during the development of the inflammatory answers. It comes secreta from linfociti T, monocites and macrofagi. This molecule regulated the inflammatory answers and has immunosoppressiva activity. Since the presence of a badly controlled inflammatory answer promotes the cardiovascular diseases, the IL-10, having a immunosoppressiva action, assumes an important and protecting role in the pathogeneses of the cardiocircolatorie diseases. Many studies have studied the present polimorfismo in the promotore region of the gene of the IL-10 in position -1082. Such polimorfismo consists in the substitution of one G (guanina) with one To (adenina). It is useful to remember that studies in vitro have suggested that the presence of the allele To is associated to one minor production of the IL-10 molecule. And emerged that the presence of genotype AA increases the risk to develop infarct to the myocardium, in other words the bearers of such genotype have a greater risk to develop cardiovascular pathologies regarding not the bearers. Murakozy (2001) J Mol Med 79, 665.

 

Factor of tumorale necrosis alpha (TNFα): polimorfismo -308 G-A

The gene factor of tumorale necrosis alpha (TNFα) is situated on chromosome 6 and codifies for omonima the protein. The TNFα is one pleiotropica for-inflammatory citochina that is in a position to carrying out numerous regulation function on the of immunity answers. The TNFα is also a mediating important of the inflammatory answers is acute that chronic. The concentration of the TNFα increases during the vascular damages produced from the formation of thrombi This factor promotes the endoteliali cells damaged stimulating them to produce adhesion molecules. Therefore favoring the adhesion to the endoteliali cells the TNFα is behaved as a promuovente factor the aterogenesi and the vascular damage cause of the infarct. The gene of the TNFα has varies situated polimorfici, between which a present polimorfismo in the promotrice region of the gene in position -308. This polimorfismo consists of one substitution of one G (guanina) with one To (adenina). Studies in vitro have put in evidence that the presence of the allele To is associated to one greater production of the same molecule. Our studies of clinical fisiopatologia have indicated that this polimorfismo turned out to be a marker for the cardiovascular diseases. Analyzing to the obtained data genotipizzando a group of patients with infarct to the myocardium and relative control group, it can be asserted that this genotype turns out to be a marker of risk of infarct to the myocardium. Herrmann Eur J Clin Invest. 1998 Jan; 28 (1): 59-66.

 

ANTI-OXIDANT ACTIVITY AND DETOSSIFICAZIONE

The anti-oxidant activity helps to fight the damages caused from the free radicalses, (RL) that they represent the refuse of the reactions of the human metabolism. The RL are practically the product of the metabolic biotrasformazione that our practical organism through the elaboration of the alimony that daily we eat. Such molecules RL are highly reactive and can induce a premature aging of the woven ones, from the skin to the inner organs, of the cardiovascular veins and arteries, diseases like ictus and cardiac infarct, until highly degenerate diseases like some types of tumor. Some present polimorfismi in specific geniuses can alter the production and the function of enzymes anti-oxidants.

 

Superossido dismutasi employee manganese (MnSOD): polimorfismi C (- 28) T and T175C

The superoxide dismutasi employee manganese (MnSOD), a mitocondriale anti-oxidant enzyme that catalyzes the conversion of the radicals superoxide in hydrogen peroxide. The MnSOD is codified from gene SOD2 localized to the locus 6q25. The gene introduces two polimorfismi, C (- 28) T and T175C: the polimorfismo C (- 28) T inside influences the intracellular distribution of the enzyme, preventing the income of this last one of the mitocondri. Such polimorfismo has been associated to a greater risk of development of some pathologies, those in particular cardiovascular ones. However it is the absence of the polimorfismo, and not its presence, to favor the development of such pathologies. The favorable effect of the presence of such polimorfismo has had to the fact that the enzyme remains works them, but distributed inside of the cell instead that to be concentrated in the mitocondri. The risk of insorgence of aforesaid pathologies diminishes with one greater introduction with the rich food diet of anti-oxidants. Polimorfismo T175C, instead, reduces the stability of the active enzyme of approximately 3 times.

 

Superossido Dismutasi (SOD3): polimorfismo C760G

The SOD3 is the main anti-oxidant enzyme of the walls of is gone blood. The levels more elevate you than SOD3 they are finds to you in the heart, the placenta, the pancreas and lungs. It moderates levels to you of SOD3 are also found in kidneys, muscles and liver. And' demonstrated state that polimorfismo C760G determines the release of enzyme SOD3 from the walls of is gone in the blood and is associated to one reduction of the tissutale anti-oxidant activity. That can contribute to the development of coronariche pathologies. Sandstrom, 1994, J. Biol. Chem. 269:19163 - 19166

 

Glutatione S-transferasi
The glutatione S-transferasi (GSTs) is a family of isoenzimi detossificanti that catalyzes the coniugazione of several toxic molecules with the glutatione rendering them little reactive and more easy dismissable from the organism. Such enzymes are codify from polimorfici geniuses comprising 5 classes to you: alpha, Devout, Mu, Theta and Zeta.
Glutatione S-transferasi P1 (GSTP1): polimorfismi I105V and A114V
, Two recently common polimorfismi of gene GSTP1 have been associate you to one consisting diminuizione of the activity of the enzyme. One of these polimorfismi, I105V, is characterized from a single substitution A>G to level of nucleotide the 313 and determines to level of the protein one aminoacidica substitution alanina>valina in position 105; the other polimorfismo, A114V, are characterized from a single substitution C>T to level of nucleotide the 341 and determine to level of the protein one aminoacidica substitution isoleucina>valina in position 114. The varying GSTP1 105Val has one frequency of 33% between the Caucasica population with a 14% of omozigoti.

 

Glutatione S-transferasi mu, M1 (GSTM1): delezione of the gene

This polimorfismo, characterized from the delezione of the greater part of the codifying region of the gene, determines one loss of functionality of the enzyme.

 

Glutatione S-transferasi theta, T1 (GSTT1): delezione of the gene

This polimorfismo, characterized from the delezione of the greater part of the codifying region of the gene, determines one loss of functionality of the enzyme. And' state moreover associated with an increased risk of tumor to lungs, laringe, blister, prostate and tumor of the cervix uterina.

 

BONY METABOLISM AND OSTEOPOROSIS

The osteoporosis represents the most frequent metabolic disease of the skeleton, characterized from a reduction of the bony mass and from an alteration of the microarchitecture which it achieves an increase of the embrittlement and the susceptibility to the fractures.
From much time it has already been verified a familiarità for the osteoporosis, however only during the last few years they are begins studies to you you turn to identify and to characterize the genetic members of such disease. The peak of bony mass that is observed between the 20 and 30 years of age is determined in great part from pure genetic factors like the speed with which the bony mass is reduced as a result of the menopause or to the aging. Moreover during the life risk factors can be accumulateed acclimatize them that they can turn out determining for rebelling of the disease.
Therefore the pathogeneses of the osteoporosis are the result of complex interactions between genetic predisposition and risk factors acclimatize them. The genetic factors play an important role in the pathogeneses of the osteoporosis and are represent you from the pool of geniuses that regulate the expression of the characters legacies to the development of pathology (mass and bony microarchitecture). The factors return of soccer and vitamin D), alcool consumption, tobacco and coffee, physical activity, drug assumption acclimatize comprise them alimentary habits (that interferes with the fosfo-calcic metabolism and above all exercises a selective effect on the genetic characteristics of the individual. In fact, although various infuences are obvious acclimatize them on determination and maintenance of bony mineral density (BMD), studies on binoculars and osteoporotiche families indicate that the genetic contribution to the pathogeneses of the osteoporosis is in charge of the 75-85% of the interindividuale variability of the BMD.
Polimorfismi genetic combinable to the osteoporosis.


The characterization of the genetic markers legacies to the ereditarietà of one low bony mineral density could allow to identify prematurely the susceptible individuals to develop osteoporosis. In this way a prevention aimed with specific therapies could be activated and modifications to the style of life, such to reduce to the maximum the risk acclimatize them in the individuals genetically predisposed to develop the disease.


From 1995 today they have been begins various studies to you actions to identify and to characterize polimorfismi in various geniuses correlates you to the bony metabolism: such analyses have the scope to evidence correlations between the varying presence of one determined allelica and one situation of reduced density of bony mass. Various polimorfismi have been until to hour identify and analyze to you to you: inside of the geniuses that they codify for the receiver of the vitamin D (VDR), Collagene IA1 (COLIA1), receiver of calcitonina (CTR) and receiver of estrogens (ESR). It turns out obtained from these studies allow to you to assert that the osteoporosis is a poligenica disease, therefore a surer determination of the predisposition to the disease demands the analysis of the various polimorfismi.
Receiver of the Vitamin D (VDR): polimorfismi Fok1, BsmI, and TaqI.


The Vitamin D promotes the internal and renal absorption of soccer and is indispensable for the development and the maintenance of the bony mass. The vitamin D also is been involved in the processes of control of the proliferation and the cellular differentiation, let alone in the immuno-modulation. In the immune system, as an example, the vitamin D promotes the differentiation of monocites and inhibits the proliferation of the linfociti ones through the increzione of citochine like IL-2, the IL12 and the interferon - γ. In some types of cells of carcinoma, the vitamin D has demonstrated a antiproliferativa activity.
The effects of the Vitamin D are mediated from its receiving nuclear (VDR), than form a eterodimerico complex with the receiver of retinoico acid and interact with the transcription factors. VDR (12q12-14) codifies for a protein of 427 amino acids (aa), than it regulated the transport and the steady state of soccer and has been proposed like the locus to greater genetic effect on the BMD in the association studies. Situated polimorfici in region 3' of human gene VDR are present various identify to you from the endonucleasi of restriction TaqI and BsmI, and a polimorfica other varying, recognized from FokI, to level of the presumed one codone of beginning of the transcription in esone the 2. The alleli they come respective calls T-t, B-b and F-f to you: the very small letters identify the presence of the situated one of restriction and the capital letters indicate the such absence of situated. Such polimorfismi can condition the answer to several dietetic members with possible risks of development of pathology.


By now an involvement is wide demonstrated works them of the alleli of the VDR in the steady state of soccer and the mineralization of the bone. The studies begin them have concurred to find the interaction between the gene of the VDR, the absorption of soccer and the levels of soccer in the diet. The alleliche variations of gene VDR explain for 70% the genetic effects on the bony density.


The polimorfismo Fok1 consists in one nucleotidica substitution T-C to level of the codone of beginning of the translation of gene VDR (ATG®ACG). Such polimorfismo determines the translation of three amino acids from the situated one of beginning of the translation of the gene with consequent alteration of the relative protein, lacking three amino acids. Nucleotide T comes also defined allele f, while nucleotide the C comes defined allele F. the combinations of these alleli puo to produce genotypes ff (TT), Ff (CT) and FF (CC). Genotype FF (short shape) provokes an increase of the activation of the transcription. The genotype ff has been associated to one low lumbar BMD in women Hispanic-Americans in postmenopausal age, Japanese, North Americans and Italians.
Also the factors acclimatize them, like the assumption of every day soccer, can modulate the effects of the genotypes of FokI on the BMD. It turns out obtained from all these studies to you of association show as the polimorfismi of VDR by themselves are not marking genetic profits in order to assign the risk of Osteoporosis, although they turn out very useful in order to explain the variability of the BMD observed in the population.


The polimorfismo BsmI, localized in introne the 8 of gene VDR and consisting in a nucleotidica variation ACTS, is associated instead to the variation of the stability of transcribed and to one the lessening of the value of the BMD. The nucleotide To it comes also defined allele B, while nucleotide G comes defined allele b. The combinations of these alleli puo to produce the genotypes BB (AA), Bb (AG) and bb (GG). The density values more elevate are turn out to you to you to cargo of the allele b, while less frequent allele B has turned out associated with inferior values of BMD. Therefore genotype BB would predispose to a low level of bony mass. Moreover, some studies have demonstrated that genotype BB predisposes to a reduced absorption of soccer to internal level.
The polimorfismo TaqI, localized in esone the 9 of gene VDR, to level of codone the 352, consists in one nucleotidica variation T-C. Nucleotide T comes also defined allele T, while nucleotide the C comes defined allele t. The combinations of these alleli puo to produce genotypes TT (TT), Tt (TC) and tt (CC). Such polimorfismo has been associated to an increase of the turnover of the bony cells with consequent increase of the risk of one reduced BMD and osteoporosis.


Various other pathologies have been correlated to the association with the aforesaid polimorfismi in gene VDR, such from being able to influence the expression or the function of the protein. In particular, such polimorfismi (Fok1, BsmI, and TaqI), can condition the answer to several dietetic members with possible risks of development of pathology. In literature some jobs are famous that correlate the association of polimorfismo VDR Fok1 with genotype FF, the risk of development of the carcinoma of the colon, in connection with the contribution of soccer and fat person in the feeding. In particular, it has been evidenced like, although alimentary soccer or the fat person does not correlate normally with the risk of development of carcinoma of the colon in the subjects with genotype FF, those with genotype to multiple allelica combination ff/Ff, a diminished contribution of soccer or of the fat person in the feeding it would increase such risk. For individuals with genotype ff and poor diet of fat person and soccer, the risk of development of the carcinoma of the colon was of approximately 2.5 times greater regarding the others. Morrison ET to (1994) 367 (6460): 284-7. I plowed (1997) J Bone Miner Res 12, 915.

 

Collagene of type I (COLIA1): polimorfismo introne 1 2046G-T

The collagene of type it is is greater organic member (90%) of the bony matrix. In the osteoporotici subjects the collageniche chains are normal, however it has been identified a polimorfismo in the situated regolator of gene COLIA1 that seems to be more frequent regarding the normal controls. This polimorfismo, than is found in the situated one of tie for the transcription of factor SP1 in the first one introne of the COLIA1, turns out to be not only associated with the bony mass but also with the osteoporotiche fractures in various caucasiche populations. This makes yes that the COLIA1 acquires particular interest, from the moment that the association with the fractures is more strongly than that one between genotype and bony mass. It is from emphasizing also that this polimorfismo is almost absent in the populations of Asia and Africa, where moreover more lowland is the incidence of osteoporotiche fractures.
Various studies on the COLIA1 demonstrate that the genetic effect of the COLIA1 strongly is associated with the reduced values of bony mass and the relation appears more grip to level of the column. In particular allele T (s), is in eterozigosi G/T (Ss) that in omozigosi T/T (ss) appears more frequent in the subjects with associated serious osteoporosis to the vertebral fractures. Therefore it has been suggested that the COLIA1 can predispose to the fractures influencing determining others of the fratturativo risk like the quality of the bone or geometry of the skeleton. It is not from excluding that the subjects more to risk with genotype ss have a altered production of collageno with consequent reduction of the peak of bony mass and probably of the thickness of the trabecole. The hypothesis that the genotype ss is associated to a altered production of the collageno moreover turns out in agreement with previous istomorfometrici data second which the subjects with vertebral fractures have one reduced ability to bony formation. Grant (1996) Nat Genet 14, 203
 

Receiver of calcitonina (CTR): polimorfismo PRO463LEU

An other more recently studied gene in the osteoporosis is that one of the receiver of calcitonina (CTR). The calcitonina is a hormone implied in the resorption of the bone and acts through specific present receivers in wide number on the osteoclasti. And' identified state a polimorfismo of the gene of the CTR consisting in one nucleotidica variation C-T to level of codone the 463 (PRO463LEU). Such mutation has been associate, in conditions of omozigosi (genotype TT, 463LEU) to reduction of the bony mass. Masi (1998) Biochem Biophys Res Commun 248, 190
Estrogenico receiver 1 (ESR1): polimorfismi PvuII (IVS1-397 T/C) and XbaI (IVS1-351 A/G)
The estrogens are indispensable for the acquisition of the peak of bony mass in both seies and for its maintenance in the adults. Associated pathological conditions to a premature deficit of estrogens accelerate the loss of the bony mass. The estrogenico deficit is the root cause of postmenopausal Osteoporosis and plays an important role also in the senile Osteoporosis, causing in both cases one greater incidence of fractures due to the embrittlement of boneses. The two isoforme of the estrogenico receiver (ER-beta and ER-alpha) are codified from two various geniuses (ESR2 and ESR1) with woven distribution specific and have various abilities in tying ligando (estrogenic and antiestrogenic) and in the activation of the transcription of the geniuses the target. Various observations show the involvement of these receivers in the determination of the BMD in both seies. In gene ESR1 (6q25) they have been described various polimorfismi, but all the association studies are focused on 2 of they, localize to you to level delll' introne 1 (recognized from PvuII and XbaI and call respective P-p and X-x to you, based on the presence or absence of the situated one of restriction).
The polimorfismo PvuII is localized in introne the 1 of gene ESR1 and consists in one nucleotidica variation T/C in position -397. Nucleotide T comes also defined allele p, while nucleotide the C comes defined allele P. the combinations of these alleli puo to produce genotypes pp (TT), Pp (CT) and PP (CC). Genotype PP is associated to one recettoriale dysfunction with reduced answer to endogenous estrogens, one lower BMD and a greater risk of Osteoporosis.
The polimorfismo XbaI is localized in introne the 1 of gene ESR1 and consists in one nucleotidica variation A/G in position -351. The nucleotide To it comes also defined allele x, while nucleotide G comes defined allele X. the combinations of these alleli puo to produce i genotypes xx (AA), Xx (GA) and XX (GG). And' be found an association between genotype XX a greater risk of fracture through an BMD-independent mechanism.




 

 --- IMPORTANT ADVISE ---

 

The scientific topics published above are addressed to the operating ones.

For the patients the information available in these pages have only an indicative value

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