2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
P06.078
the association between gene polymorphism of cytochrome
P450 2D6 and behavioral characteristics
V. A. Shleptsova1 , J. Shchegolkova2 , A. G. Tonevitsky3 ;
1Faculty of basic medicine, Moscow State University, Moscow, Russian Federation,
2Biological faculty, Moscow State University, Moscow, Russian Federation,
3Russian research institute of sport and physical education, Moscow, Russian
Federation.
The cytochrome P450 2D6 (CYP2D6) enzyme is involved in the hepatic
metabolism of many drugs and other exogenous substances . There
are a little evidences that CYP2D6 involves in metabolism of endogenous
psychoactive substances and expresses not only in liver but
also in the brain. Therefore it may influence on psychological process.
It has been shown that there are significant differences in personality
between extensive and poor metabolizers .
In our investigation we investigated an association of gene polymorphism
of CYP2D6 and personality traits . 160 healthy subjects took part
in the study (women - 82, men - 78) . There were tested by different
psychological questionnaires which examine aggression, impulsivity,
anxiety and others and also by psychophisiological measurements .
We genotyped with PCR-method any gene variations of CYP2D6:
CYP2D6*1, CYP2D6*2 (C2850T), CYP2D6*4 (G1934A), CYP2D6*10
(C100T) We showed that CYP2D6 poor metabolizers (CYP2D6*4, CY-
P2D6*10) had significantly higher level of verbal aggression (p=0.04)
and inability of stopping aggression (p=0 .04) and had more pleasure
of aggression (p=0 .02) than extensive metabolizers (CYP2D6*1, CY-
P2D6*2) . Furthermore, this relationship expressed to the same extent
both at men, and at women .
Association between CYP2D6 gene polymorphism and personality
characteristics can indicate on influence cytochrome activity on
neuromediator`s metabolism in brain .
P06.079
cytokine genes polymorphisms are associated with essential
hypertension in tatars from Bashkortostan, Russia
Y. R. Timasheva1 , T. R. Nasibullin1 , A. N. Zakirova2 , O. E. Mustafina1 ;
1 2 Institute of Biochemistry and Genetics, Ufa, Russian Federation, Bashkir
State Medical University, Ufa, Russian Federation.
Cardiovascular disease is the leading cause of death in the Western
world . Recently inflammation was proved to be the main substrate underlying
the development atherosclerosis . Cytokines mediate interactions
of all cells participating in atherogenesis . However, the role of
certain cytokines genetic variants on disease risk is not well understood.
We tested the hypothesis that specific genetic polymorphisms
of some cytokines are associated with increased risk of essential hypertension
(EH) and its cardiovascular complications .
355 patients with EH and 343 unrelated normotensive individuals
without family history of cardiovascular disease were enrolled in the
study . Both patients and control originated from Tatar ethnic group
from Bashkortostan, Russia . DNA was isolated from peripheral venous
blood . Genotyping was performed using polymerase chain reaction
and restriction analysis . Statistical analysis was performed using
Fisher’s exact test. Odds ratios with 95% confidence interval were also
calculated .
We have shown that IL-10 -627*C/*C genotype is associated with decreased
hypertension risk (OR=0 .53, CI: 0 .22-0 .78). TNFA -308*G/*G
was found to be protective against stroke in hypertensive patients
(OR=0 .48, CI: 0 .24-0 .97) . 1159*A/*A IL12B genotype was also associated
with lower stroke risk (OR= 0 .43, CI: 0 .21_0 .9) .
We demonstrate that common genetic variants of IL10, TNFA and
IL12B genes are associated with the risk of EH and its complications .
Our data suggest a role for cytokine genes polymorphisms in cardiovascular
disease .
P06.080
strong linkage disequilibrium for the frequent GJB 35delG
mutation in the Greek population
H. Kokotas 1 , L. Van Laer 2 , M. Grigoriadou 1 , V. Iliadou 3 , J. Economides 4 , S.
Pomoni 1 , A. Pampanos 1 , N. Eleftheriades 5 , E. Ferekidou 6 , S. Korres 6 , A. Giannoulia-Karantana
7 , G. Van Camp 2 , M. B. Petersen 1 ;
1 Institute of Child Health, Athens, Greece, 2 University of Antwerp, Antwerp,
Belgium, 3 AHEPA Hospital, Thessaloniki, Greece, 4 ‘Aghia Sophia’ Children’s
Hospital, Athens, Greece, 5 St. Loukas Hospital, Thessaloniki, Greece, 6 Athens
University, Athens, Greece, 7 Athens University Medical School, Athens, Greece.
Approximately one in 1,000 children is affected by severe or profound
hearing loss at birth or during early childhood (prelingual deafness) .
Up to forty percent of autosomal recessive, congenital, severe to
profound hearing impairment cases result from mutations in a single
gene, GJB2 . The 35delG mutation accounts for the majority of GJB2
mutations detected in Caucasian populations and represents one of
the most frequent disease mutations identified so far. Some previous
studies have assumed that the high frequency of the 35delG mutation
reflects the presence of a mutational hot spot, whilst other studies support
the theory of a common founder . Greece is amongst the countries
presenting high frequency of the 35delG mutation (3 .5%), and a recent
study raised the hypothesis of the origin of this mutation in ancient
Greece . We genotyped 60 Greek deafness patients homozygous for
the 35delG mutation for six single nucleotide polymorphisms (SNPs)
and two microsatellite markers, mapping within or flanking the GJB2
gene, as compared to 60 Greek hearing controls . A strong linkage
disequilibrium was found between the 35delG mutation and markers
inside or flanking the GJB2 gene, at distances of 34 kb on the centromeric
and 90 kb on the telomeric side of the gene, respectively .
Our study supports the hypothesis of a founder effect and we further
propose that ethnic groups of Greek ancestry could have propagated
the 35delG mutation, as evidenced by historical data beginning from
the 15 th century BC .
P06.081
Detoxification system gene variants and small-for-gestationalage
births
N. Nabieva 1 , T. Ivashchenko 2 , N. Shabalov 1 , V. Baranov 2 ;
1 Medical Pediatrics Academy, St.Petersburg, Russian Federation, 2 Ott’s institute
of Obstetrics and Gynecology, St.Petersburg, Russian Federation.
Small-for-gestational-age (SGA) is defined as birth weight below the
10th percentile according to gestational age and sex based on national
standards. Little is known about the role of detoxification system gene
variants as risk factors for SGA births . Only a few studies have considered
the direct role of polymorphic xenobiotic-metabolizing genes in
fetal growth . GSTM1 and GSTT1, in the GST family, are both involved
in the biotransformation of a wide range of reactive toxic and mutagenic
compounds, including ROS oxygen species and components of
tobacco smoke . GST enzymes are present in large amounts in the
placenta in early pregnancy and are expressed early in embryonic
development . The polymorphisms of xenobiotic-metabolizing genes
(GSTM1, GSTT1, NAT2) responsible for xenobiotics conjugating enzymes
of Phase II detoxification system were studied by PCR-RFLP in
SGA infants and control group newborns .
The genotypes distribution for NAT2 gene was identical in controls
group and in group of SGA patients . The analysis of genotypes distribution
for polymorphism and GST M1 in patients and in controls has
not revealed significant differences.
The frequency of GSTT10/0 genotype was significantly higher in
group of patients compared to controls (34% versus 10% respectively,
p=0 .003) . Concordance of both GSTT1 0/0 and NAT2 S/S genotypes
were found in 17 .2% of patients and was almost 4 times more compared
to only 4% in control (p=0 .01) . The 37% of patients had at least
two functionally impaired genotypes for studied genes .
The study provides new information on the role of polymorphic detoxification
genes in development of SGA.
P06.082
Analysis of the association between LEcAm-1 P213s
polymorphism and EsRD in diabetic patients
C. M. Tecuceanu, D. Cimponeriu, P. Apostol, M. Stavarachi, M. Toma, L.
Gavrila;
Institute of Genetics, Bucharest, Romania.
Mutations in lyam-1 gene (1 q23-q25) may predispose to phenotypes
that can aggravate the evolution of vascular complications in diabetic
patients, including renal disease .
The purpose of this case-control study was to estimate the association
of LECAM P213S polymorphism with end-stage renal disease (ESRD)
in diabetic patients .
Clinical information and biological samples were collected from dialyzed
type I diabetic patients (n=100, M:F = 50:50) and healthy subjects
(n=200, fasting glycemia 93 .2±8 .2 mg/dl) . Healthy subjects were
0