2009 Vienna - European Society of Human Genetics

Evolutionary and population genetics, and Genetic epidemiology
in Tehran to 27.1% in Shiraz. Overall, there were no significant differences
in allele frequencies across cities or ethnic groups. However,
the allele frequency of the COX-2 genotype in the Tehran population
was significantly different from that of the Shiraz population (p value
= 0.048). The results indicated that the prevalence of this COX2 polymorphism
did not differ in healthy populations from Iran and Baghdad.
Thus, this polymorphism may be a suitable target for genetic research
in the field of inflammatory diseases among Iranian and Arab populations.
P10.15
study of association between polymorphism of 5 genes and
crohn’s disease in Russian population
Y. A. Nasykhova 1 , N. V. Semenov 2 , T. E. Ivaschenko 1 , A. Y. Baranovskii 2 , V. S.
Baranov 1 ;
1 Ott’s Institute of Obstetrics & Gynecology, St-Petersburg, Russian Federation,
2 Medical Academy of Postgraduate study, St-Petersburg, Russian Federation.
Crohn’s disease (CD) is a chronic relapsing inflammatory bowel disorder
which etiology remains unknown. At present the incidence of this
disorder increases in the world. Therefore CD is thought to be one of
the serious problems in the gastroenterology.
Allele and genotype frequencies of 8 polymorphic variants of 5 genes
such as NOD2/CARD15 (Arg702Trp, Gly908Arg, Leu3020InsC), TNFA
(-238G/A, -308G/A), VDR (Taq-1), IL-4 (C-590T), IL-4R (Q576R) were
studied in CD patients (102 individuals) and in controls (112 individuals).
The patients and the control individuals were recruited in the North-
West region of Russian Federation. The frequency of 3020InsC allele
of NOD2/CARD15 gene was 3-fold higher in CD patients compared
to controls (18% against 6%, p=0.006). In patients with complicated
forms of CD the 3020InsC allele was significantly more frequent (27%)
compared to patients with inflammatory forms of CD (8,3%; p=0,02).
26,5% of CD patients were carriers of the rare allele -308*A for -308G/
A polymorphism of TNFA gene and only 8% of controls (p=0.0004).
The frequency of heterozygote genotype -308*GA was significantly
higher in CD patients than in controls (24.5% against 8%, p=0.0004).
Frequency of 576*RR genotype of IL-4R gene was significantly higher
in CD patients (11,7%) in comparison with controls (1,4%; p=0,016,
OR=9; 95% CI:1.15-71.47).
Thus, 3020InsC, -308*A alleles and 576RR genotype could be the risk
factors of CD in Russian population. We suggest that DNA-testing of
polymorphic variants of NOD2/CARD15, TNFA, IL-4R genes is important
for the presymptomatic diagnostics of Crohn’s disease.
P10.16
cYP2c19*2, cYP2c19*3 and cYP2c19*4 alleles frequencies in a
Romanian population
A. P. Trifa, R. A. Popp, M. S. Militaru, T. O. Crisan, D. R. Arbore, I. V. Pop, A.
D. Buzoianu;
University of Medicine and Pharmacy, Cluj-Napoca, Romania.
CYP2C19, a member of the cytochrome P450 superfamily, metabolizes
around 15% of the clinical relevant drugs. Its coding gene, CYP2C19,
has been shown to be polymorphic, two prominent alleles, CYP2C19*2
and CYP2C19*3, well studied in many populations, being associated
with a poor metabolizer phenotype. The CYP2C19*4 allele, which is
also associated with a poor metabolizer status is less characterized in
the Caucasian populations. Taking into consideration the lack of data
regarding the frequencies of these three CYP2C19 alleles in Romania,
the aim of this study was to provide a first evaluation of these alleles on
a Romanian population group. The CYP2C19 alleles were studied in
200 healthy unrelated individuals. PCR-RFLP assays were employed
for the study of each CYP2C19 allele, plus an extra tetra-primer PCR
assay used to randomly verify the results obtained with PCR-RFLP
for CYP2C19*2 and CYP2C19*3 alleles. CYP2C19*2 was observed
in heterozygous state in 49 individuals (24.5%) and in homozygous
state in 3 individuals (1.5%), while CYP2C19*3 allele was not demonstrated
in any individuals. CYP2C19*4 was seen in heterozygous
state in one individual (0.5%), who was heterozygote for CYP2C19*2
as well. Thus, the allele frequencies for CYP2C19*2, CYP2C19*3 and
CYP2C19*4 were 13.75%, 0% and 0.25%, respectively. Overall, 4 individuals
(2%) included in this study are predicted to be CYP2C19
poor metabolizers. Genotyping for CYP2C19 variants before starting
the medication with drugs substrates for CYP2C19 could reduce the
impact of adverse drug reactions and treatment failures, based on an
individual, optimized drug therapy.
P10.17
study of DFNB59 gene mutations in exon 2 and 4 in association
with deafness using PcR-RFLP in a Province of iran
M. Taherzadeh Ghahfarrokhi1 , E. Farrokhi2 , J. Saffari Chaleshtori2 , S. khademi2
, S. Asadi2 , F. Shayesteh2 , G. Mobini2 , N. Parvin3 , M. Banitalebi2 , R. Hagihoseini
Baghdadabadi4 , H. Nazem4 , M. Hashemzadeh Chaleshtori2 ;
1Tehran Payame Noor Univ and Cellular and Molecular Research Center Univ.
of Med.Sci, Shahrekord, Islamic Republic of Iran, 2Cellular and Molecular Research
Center Univ. of Med.Sci, Shahrekord, Islamic Republic of Iran, 3Plant Reaserch Center, Shahrekord Univ. of Med.Sci, Shahrekord, Islamic Republic
of Iran, 4Biochemistry Dept., Payame noor Univ, Tehran, Islamic Republic of
Iran.
Background and aim: Hearing loss is a heterogeneous disorder and
may be due to genetic or environmental cause. A novel gene, DFNB59
encods pejvakin has been very recently shown to cause neural deafness.
This study aims to determine the frequency of DFNB59 gene
mutations in exon 2 and 4 in 100 patients negative for GJB2 mutations
in a province of Iran.
Methods: In this descriptive-lab based study we investigated the frequency
of DFNB59 gene mutations in exon 2 and 4 of the gene.
DNA was extracted from all patients following the standard phenol
chloroform procedure. The two mutations T54I and R183W was determined
using PCR-RFLP procedure.
Results: The AF1III restriction enzyme digested the related restriction
site in all of the 100 samples examined. Also, SsiI restriction site were
digested in all of the 100 samples. These data indicate that no T54I
and R183W mutations were not detected in deaf individuals tested.
Conclusion: Based on data from the present study and previous study,
we conclude that DFNB59 gene mutations have a very low contribution
to deafness in patients in a province of Iran. However, we examined
only 2 DFNB59 mutations in 100 patients and to determine the
role of this gene in developing deafness the entire coding region and
promoter of the gene need to be investigated in more samples.
P10.18
DNA repair gene polymorphisms in dialysis patients
M. Guven1 , B. Batar1 , G. S. Güven2 , M. R. Altıparmak3 , A. Tunçkale3 , S. Trablus4
, M. Seven2 , E. Yosunkaya2 , A. Yüksel2 ;
1Department of Medical Biology, Cerrahpasa Medical School University of
Istanbul, Istanbul, Turkey, 2Department of Medical Genetics, Cerrahpasa Medical
School University of Istanbul, Istanbul, Turkey, 3Department of Internal
Medicine, Cerrahpasa Medical School University of Istanbul, Istanbul, Turkey,
4Department of Nephrology, Istanbul Training and Research Hospital, Istanbul,
Turkey.
Patients with end-stage renal failure, whether on conservative or haemodialysis
therapy, have a high incidence of DNA damage, therefore
the potential involvement of DNA damage and its repair are of particular
interest. Polymorphisms of DNA repair enzymes may affect
repair efficiency and modulate cancer susceptibility. In this study, we
aimed to determine the frequency of four polymorphisms in two DNA
repair enzyme genes, xeroderma pigmentosum complementation
group D (XPD) and X-ray cross-complementing group 1 (XRCC1), in
65 patients undergoing hemodialysis, and 61 subjected to peritoneal
dialysis, matched for gender and age with 60 controls. We used polymerase
chain reaction (PCR) and restriction fragment length polymorphism
(RFLP), to analyze XPD Asp312Asn, XPD Lys751Gln, XRCC1
Arg194Trp, and XRCC1 Arg399Gln polymorphisms.The genotype distributions
in the patients and controls were in Hardy-Weinberg equilibrium
for each polymorphism. For each polymorphism there was no
significant difference in the genotype distribution between the control
group and the dialysis patients, or between the HD and the PD patients
(p>0.05). Allele frequencies were also not statistically different
between the groups (p>0.05). We conclude that DNA repair gene polymorphism
is not associated with renal failure.
P10.19
Analysis of dopamine D2 receptor (DRD ) gene polymorphisms
in cannabinoid users
M. Nacak 1 , A. Baransel Isir 2 , S. Oguzkan-Balcı 3 , S. Pehlivan 3 , A. Aynacioglu 1 ,
N. Benlier 1 ;
1 University of Gaziantep, Faculty of Medicine, Department of Pharmacology,