2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
py, Novosibirsk, Russian Federation.
Due to key role of mitochondria in cell energy production, mitochondrial
DNA is considered as candidate locus for different common diseases
as well as for predisposing to longevity. Some associations of different
mtDNA haplogroups with longevity were shown in European populations.
To explore possible associations of mtDNA polymorphisms with
longevity in population of Siberian part of Russia, we have studied
mtDNA in samples of long-livers (>90 years old) from Tomsk and Novosibirsk
(N=235) by sequencing HVS1 region and restriction analysis
for haplogroup assignment. We have compared frequencies of main
European haplogroups (H, H1, U4, U5, K, J, T) and some frequent
polyphyletic HVS1 polymorphisms (16189, 16311, 16362, etc) in longlivers
group with mtDNA data on Tomsk population. No significant differences
were found for haplogroups, as well as for big clusters (J+T,
U, H+HV+V). At the same time, the long-livers had higher frequency
of T16189C polymorphism (21.3% comparing to 12.2% in population,
P=0.04). There was no difference between long-livers and population
in “haplogroup composition” of the 16189C group (main contributors
were haplogroups H1 and U5). T16189C variant is known as associated
with diabetes in adults, increased body mass index and insulin
resistance. In contrast, our results suggest that this variant may have
also positive influence on fitness, thus favoring for longevity. The study
was supported by RFBR grant 07-04-01526a.
P09.075
infant c677t genotype of the mtHFR gene as a risk factor nonsyndromic
cleft lip with/ without palate
K. Ulucan1 , D. Kirac2 , T. Akcay3 , D. Javadova4 , G. Koc4 , D. Ergec5 , A. I.
Güney4 ;
1Marmara University, Faculty of Dentistry, Department of Medical Biology and
Genetics, Istanbul, Turkey, 2Yeditepe University, Faculty of Medicine, Department
of Biochemistry, Istanbul, Turkey, 3Marmara University, Faculty of Medicine,
Department of Pediatric Endocrinology, Istanbul, Turkey, 4Marmara University,
Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey,
5Maltepe University, Faculty of Medicine, Department of Medical Biology and
Genetics, Istanbul, Turkey.
5,10- Methylenetetrahydrofolate reductase (MTHFR) gene is located
on 1p36.3 and involved in folate metabolism. It has two common gene
variants, C677T and A1298C. C677T homozygosity is associated with
several congenital anomalies, mostly neural tube defects. Non-syndromic
cleft lip with/without palate (NSCLP) is one of the most common
congenital anomalies, with a prevalance of 1/1000 in Caucasians.
It is a multifactorial pathology affected from different loci and genes,
environmental factors also implicated in NSCLP. To date C677T, in the
terms of NSCLP and MTHFR, has either conflicting results or couldn’t
be replicated properly. Our aim is to determine a relation between infants’
MTHFR C677T polymorphism and (NSCLP) in Turkish population.
We have established 100 NSCLP patients without any family history
of CLP and 100 controls. PCR- RFLP method was performed for the
determination of MTHFR gene by using specific primers and Hinf I
restriction enzyme.
CC (wild type) frequencies were %39 and %41 in NSCLP patients and
controls respectively. %43 of the patients and %47 of the controls were
CT and %18 of the patients and %12of the controls were TT (mutant)
for the MTHFR C677T allele.
No statistically significant differences were detected between study
and control groups. Our study suggests that only MTHFR C677T genotyping
in infants may be a useless approach to suggest as a risk
factor for NSCLP in Turkish population.
P09.076
the mtHFR c677t polymorphism increase the risk for renal
involvement in type 2 diabetic patients
D. Cimponeriu1 , P. Apostol1 , M. Stavarachi1 , M. Toma1 , I. Radu1 , A. Craciun2 ,
N. Panduru2 , C. Serafinceanu2 , L. Gavrila1 ;
1 2 Institute of Genetics, Bucharest, Romania, N Paulescu Institute, Bucharest,
Romania.
Renal disease is one of the most common complications of diabetic
patients. Many studies suggest that MTHFR (Methylentetrahydrofolate
reductase) and TGF-beta polymorphisms increases the risk for renal
involvement in diabetic patients.
The purpose of this case-control study was to estimate the association
between MTHFR C677T and TGF-beta C-509T polymorphisms and
renal failure in diabetic patients.
Clinical information and biological samples were collected from dialyzed
patients with type I diabetes (n=116, male: 56%, dialysis: 1,6±0,8
years), type II diabetes (n=123, male: 55.28%, 2,4±1,2, dialysis:
2,3±1,2 years) or chronic glomerulonephritis (n=121, male: 49.58%,
dialysis: 1,7±0,9 years) and from healthy subjects (n=494, fasting glycemia
93.2±8.2 mg/dl). Healthy subjects were selected to be matched
for age and gender with patients. All subjects selected for this study
were unrelated Romanian Caucasians.
Blood samples from all subjects were used for DNA extraction. DNA
samples were used for genotyping TGFb -509 and MTHFR C677T
polymorphisms using PCR and PCR RFLP methods.
In the case of MTHFR C677T the distribution of genotypes remains
significant only when T2DM patients and controls were compared
(p=0,019). The results showed no association between TGFbeta and
the risk for renal failure in diabetic or nondiabetic patients (OR~1).
In conclusion, our study demonstrates:
1. The MTHFR C677T is associated with ESRD in type 2 diabetic patients.2.
TGF-beta genotypes are not significant risk factors for development
of ESRD.
(Project: Romania, PNII-IDEI, code 2150)
P09.077
An investigation of polymorphisms in ctLA-4 gene for
association with multiple sclerosis in iranians
M. R. Noori-Daloii, A. Heidari, M. Keramati-Pour, A. Rashidi-Nejad, A.
Amirzargar, A. Sahmani;
Tehran Univ. of Medical Sciences, Tehran, Islamic Republic of Iran.
Multiple sclerosis (MS), a chronic inflammatory demyelinating disease
of the central nervous system is believed to have a T cell-mediated
autoimmune etiology. The cytotoxic T lymphocyte antigen 4 (CTLA-4)
gene is a strong candidate for the involvement in autoimmune diseases.
To examine the genetic association of the CTLA-4 gene locus
with MS, in a case-control design, we analyzed three single nucleotide
polymorphisms (SNPs) of the CTLA-4 gene including -318 C/T, +49A/
G and CT60 in 135 unrelated Iranian relapsing-remitting MS patients
and 135 healthy subjects using PCR-RFLP method. The overall genotype
frequencies of -318 CC, CT and TT were 79.6%, 18.9% and 1.5%,
respectively. Regarding the +49A/G SNP the overall genotype frequencies
for AA, AG and GG were 29.6%, 53% and 17.4%, respectively and
for CT60 SNP the overall genotype frequencies for AA, AG and GG
were 19.3%, 50.7 and 30%, respectively The distribution of CTLA-4
(-318 C/T) genotype and allele frequencies did not significantly differ
between MS patients and healthy subjects. In conclusion, there may
not be any association between CTLA-4 gene polymorphisms and MS
development.
Key words: Allelic association; CTLA-4; multiple sclerosis; RFLP; Single
nucleotide polymorphism
P09.078
Polymorphisms of hemochromatosis and transferrin genes in
multiple sclerosis
N. Starcevic Cizmarevic 1 , S. Ristić 1 , L. Lovrečić 2 , J. Sepčić 3 , B. Brajenović-
Milić 1 , A. Buretic Tomljanovic 1 , M. Kapović 1 , B. Peterlin 2 ;
1 Department of Biology and Medical Genetics, School of Medicine, Rijeka,
Croatia, 2 Division of Medical Genetics, UMC, Ljubljana, Slovenia, 3 Postgraduate
Study, School of Medicine, Rijeka, Croatia.
Recent evidence has indicated a role for iron dysregulation in disease
pathogenesis. We tested the hypothesis that polymorphisms in
HFE (C282Y and H63D) and TF (C1 and C2) genes, and interactions
among these polymorphisms, influence predisposition to and clinical
presentation of multiple sclerosis (MS).
Three hundred and sixty-eight MS patients and 368 healthy controls
were genotyped by PCR-RFLP method.
Statistically significant higher frequency of the C282Y mutation carriers
was observed in patients with secundary-progressive or relapsing-remitting
MS (7.7%) than in the control group (3.8%) (p=0.026). A
significantly earlier age of onset was found in carriers of the C282Y
mutation (p=0.035). The frequency of H63D homozygotes was higher
(2.8%) in control group than in MS patients (0.7%) with borderline significance
(p=0.050). We found no corelation between H63D mutation
and disease behavior (p>0.05). We were unable to detect significant