2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
(CG), 66+/-19 kg (GG); P=0.004. This decrease in body-weight in Gallele
carriers was observed in both men and women.
P09.092
serotonergic polymorphisms in childhood onset Obsessive
compulsive Disorder
Z. Nemoda 1 , E. Kenezloi 2 , Z. Tarnok 2 , J. Gadoros 2 , M. Sasvari-Szekely 1 ;
1 Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Budapest,
Hungary, 2 Vadaskert Child and Adolescent Psychiatric Clinic, Budapest,
Hungary.
Childhood onset Obsessive Compulsive Disorder (OCD) has substantial
genetic background. The symptoms are likely to evolve as a result
of interactions of adverse environmental factors and predisposing genetic
factors. Hitherto, only the long-allele of the serotonin transporter
gene promoter polymorphism has been indicated as potential risk
factor for OCD. In the present study we aimed to investigate genetic
polymorphisms in the serotonin transporter, tryptophan hydroxylase 2
(TPH2), and serotonin 1A and 1B receptor genes.
Clinical diagnosis of 115 OCD patients was obtained by the DSM-IV
criteria, for symptom assessment the Children’s Yale-Brown Obsessive
Compulsive Scale was administered. Anxiety or mood disorder
was present in 38%, and 48% of the children had comorbid tics. Variable
number of tandem repeats in the serotonin transporter gene
(5HTTLPR in the promoter region, STin2 in the second intron) and
single nucleotide polymorphisms in the TPH2 and serotonin receptor
genes were studied. Allele- and genotype-frequencies of the OCD
clinical group as well as subgroups of OCD with/without tics or anxiety
disorder were compared to a sex matched (77.2% male and 22.8%
female) control group.
The serotonin transporter polymorphisms were associated with OCD,
more specifically with the OCD + anxiety disorder subgroup. Genotype
frequency of the STin2 was significantly different when the anxiety
present OCD group was compared to the anxiety absent OCD group
or to the control group (p = 0.04, and p = 0.05, respectively). In addition,
increased SL genotype frequency of 5HTTLPR could be detected
in this subgroup.
This work was supported by OTKA-F67784.
P09.093
AXIN contributes to cleft lip and palate in multiple populations
R. Menezes, M. L. Marazita, M. E. Cooper, T. G. McHenry, K. Bardi, C. Brandon,
A. Letra, R. A. Martin, A. R. Vieira;
University of Pittsburgh, Pittsburgh, PA, United States.
Cancer and congenital malformations occasionally may have a common
etiology. We have recently demonstrated that families segregating
oral clefts present a higher incidence of family history of cancer
and that AXIN2, a gene that when mutated increases susceptibility
to colon cancer, was associated with cleft lip with or without cleft palate
(CL/P) in a US population. In this study, we genotyped 484 families
with more than two affected cleft individuals from North America
(USA), Europe (Spain, Hungary and Turkey), Asia (China and India)
and central America (Guatemala) to test for association with AXIN2.
TaqMan chemistry was used to generate genotype data in four SNP
markers and alleles at each AXIN2 SNP were tested for transmission
distortion with CL/P using the Family-Based Association Test (FBAT).
We tested each population individually and pooled for all populations
as well as for Caucasian, Asian, and Hispanic subsets. AXIN2 markers
were associated with CL/P in the U.S. group (p=0.01), in the Spanish
cohort (p=0.04), and in the pooled dataset (p=0.02). The association
was more significant in the U.S. group when only cleft lip and palate
individuals were considered in the analysis (p=0.003). Our results
suggest that AXIN2 represents a component in the etiology of human
clefting.
P09.094
Identification of genetic risk factors for preventing osteoporosisrelated
fractures
D. Stoicanescu1 , M. Cevei2 , V. Belengeanu1 , E. Sirbu3 , B. Almajan-Guta4 ;
1University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania,
2 3 Faculty of Medicine and Pharmacy, Oradea, Romania, West University, Timisoara,
Romania, 4University “Politehnica”, Timisoara, Romania.
Osteoporosis is a polygenic disorder dependent on multiple genes and
environmental factors. It is one of the major and growing health care
problems around the world, related to the general aging of societies,
with improvement in preventive health and delay in mortality. Fracture,
the clinical outcome of osteoporosis, is also dependent on genetic factors,
with a heritability of about 25-35%. The objective of the present
study was to describe genetic epidemiological aspects of osteoporosis,
as family history may predict the disease risk in otherwise
healthy women. 62 patients were studied, mean age of 51 years, just
before or soon after menopause. 2/3 of the women who had mothers
with osteoporosis developed this disease too, which proves that the
maternal parent with osteoporosis represents an important risk factor,
unfortunately not possible to influence. About 1/3 of these women
had vertebral osteoporosis, half of them having 1 or more vertebral
fractures. Osteoporosis was developed in more than 2/3 of the cases
in which menopause was settled before the age of 45. Thus, settling of
menopause before this age is a very important cause for the release
of physiopathological mechanisms of osteoporosis. A parental history
of fracture confers an increased risk of fracture that is independent of
bone mineral density, suggesting that there is another shared component,
which influences bone fragility. These results provide an initial
epidemiological profile for osteoporosis and fracture risk besides information
useful for genetic counseling.
P09.095
Genetic associations of the antioxidative enzyme glutathione
peroxidase 1 with low bone mineral density in men
S. Jurković Mlakar 1 , J. Osredkar 1 , J. Prezelj 2 , J. Marc 3 ;
1 Institute for Clinical Chemistry and Clinical Biochemistry, University Medical
Centre Ljubljana, 1000 Ljubljana, Slovenia, 2 Department of Endocrinology,
Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, 1000
Ljubljana, Slovenia, 3 Department for Clinical Biochemistry, Faculty of Pharmacy,
1000 Ljubljana, Slovenia.
Glutathione peroxidase 1 (GPX1) is an important antioxidant enzyme
in humans. It protects human body from negative effects of reactive
oxygen species. Recently, oxidative stress has been suggested to participate
in the development of osteoporosis. Osteoblasts can produce
antioxidants such as GPX1 to protect against reactive oxygen species.
The aims of this study were to determine frequencies of genotypes of
GPX1 genetic polymorphisms and to associate with low bone mineral
density (BMD) and concentration of plasma osteocalcin of 115 men,
aged 67,96 ± 6,01 years. Each patient was examined clinically with the
measurement of BMD and concentration of plasma osteocalcin.
PCR was used to amplify two fragments in coding regions of the gene
GPX1 to determine polyalanine regions of 5, 6 and 7 trinuclotide repeats
using the DHPLC method and Pro198Leu polymorphism using
RFLP method.
The frequencies of genotypes of 115 men subjects were as follows:
5/5 (27,8%), 5/6 (19,1%), 5/7 (22,6%), 6/6 (9,6%), 6/7 (13,9%), 7/7
(7,0%) for the polyalanine repeats and CC (54,8%), CT (35,7%), TT
(9,6%) for Pro198Leu polymorphism. The genotype 6/7 is significantly
associated with a higher BMD value of femoral neck and total hip than
the 5/5, 5/6, 5/7 and 6/6 genotypes (p