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:
-
the
compounds introduced with the diet can exercise to level of the
human genome direct or indirect effects, altering the expression
and/or the structure of the geniuses;
-
the
diet can represent a factor of risk or one instrument of prevention
for degenerate pathologies;
-
the
degree in which the diet disease can influence the budget health/depends
on the genetic equipment of every individual;
-
a
nutrizionale participation based on the acquaintance of the genotype
and the state of nutrition of the individual can be used in order to
prevent or to cure pathologies.
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
and they cannot replace a medical opinion.