2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
using HBAT. AVPR1A alleles and haplotypes were also associated with
composing (p=0.0351), improvising (p=0.0364) and arranging music
(p=0.0334). Serotonin transporter gene (SLC6A4: promoter region 5-
HTTLPR) was highly associated with COMB (p=0.0084). The results
suggest that the neurobiology of music perception and production is
related to the pathways affecting intrinsic attachment behavior important
in evolution.
P09.084
No association of oestrogen receptor gene polymorphisms with
myasthenia gravis
Z. Pal 1,2 , A. Gál 1 , V. Reményi 1 , K. Pentelényi 1 , M. J. Molnár 1 ;
1 Clinical and Research Centre for Molecular Neurology, Budapest, Hungary,
2 Department of Genetics Cell- and Immunobiology, Budapest, Hungary.
Objective: Myasthenia Gravis (MG) is an autoimmune disease that effects
women more often than men, implying that sex hormones may
play a role in its pathogenesis. Our aim was to investigate the possible
role of oestrogene in the pathomechanism of MG by elavulating the
association of oestrogene receptor (OR) polymorphisms in MG.
Methods: PvuII and XbaI restriction fragment polymorphisms of the
OR gene were analyzed in 33 male and 130 female MG patients and
40 male and 134 female healthy controls. The distribution of OR genotypes
was compared between the MG patients and the healthy control
group. MG patients were divided into groups according to their OR
genotypes, then their AchR antibody status and age of onset and were
compared between the groups.
Results: The OR genotype frequency of distribution did not show any
significant differences either between male MG patients and male controls
or female patients and female controls. No association was found
between the OR status and the age of onset or AchR antibody positivity
in either of the genders.
Conclusion: Though a larger patient sample is needed, our results
suggest, that OR status does not influence MG age of onset or AchR
antibody seropositivity.
P09.085
Association of the sPiNK5 gene genotypes and haplotypes with
nasal polyposis
F. Belpinati 1 , C. Bombieri 1 , G. Malerba 1 , S. Gambardella 2 , M. D’Apice 2 , C. Corradini
3 , G. Novelli 2 , P. Pignatti 1 ;
1 Section of Biology and Genetic, University of Verona, Verona, Italy, 2 Department
of Biopathology, and Diagnostic Imaging, Tor Vergata University, Rome,
Italy, 3 Department of Otolaryngology, Catholic University of Sacred Heart,
Rome, Italy.
Nasal polyps (NP) are lesions that emanate from nasal mucosa or
paranasal sinuses, caused by inflammation, related to dysregulation
of epithelial cell proliferation. NP incidence is higher in cystic fibrosis
(CF) patients than in general population (35-45% vs 1-4%) and is
one of the major otolaryngological CF manifestations, but no particular
CFTR gene mutation was found associated with NP in CF patients.
In an our previous study the D386N-SNP in SPINK5 gene was found
associated with NP in CF patients.The aim of this study was to determine
if SPINK5 variants could modulate the development of NP in
CF patients. Five SNPs, representative of SPINK5 LD blocks, were
selected and analysed in 4 groups of subjects: 79 nonCF subjects
with NP and 39 CF patients with NP, 104 CF patients without NP and
101 controls. All CF patients have two CFTR severe mutations. Allele
and genotype frequency and HW equilibrium were calculated for each
polymorphism. An association analysis between either single SNP or
5 SNPs of the SPINK5 gene and the NP was carriedout. Haplotype
analyses were also computed.
A significant association between rs6892205 and NP was found in almost
all the analyses performed (p: 0.005-0.01) while association of
D386N was limited to CF group only (p=0.001). A preferential association
with NP was also confirmed by the haplotype analysis (p: 0.0015-
0.015). These data support the association of SPINK5 gene with NP.
It is possible to suppose for SPINK5 gene a role in the inflammatory
process involved in the pathogenesis of NP.
P09.086
maternal mtHFR polymorphisms do not predispose to neural
tube defects in india
K. G. Godbole 1 , T. Gayathri 2 , P. Smitha 2 , S. Ghule 1 , N. Memane 1 , A. Kanitkar 1 ,
G. R. Chandak 2 , N. Oza 3 , J. Sheth 3 , I. Amithkumar 4 , S. Suresh 4 , C. S. Yajnik 1 ;
1 K.E.M. Hospital and Research Center, Pune, India, 2 Center For Cellular and
Molecular Biology, Hyderabad, India, 3 Foundation for Research In Genetics and
Endocrinology, Ahmedabad, India, 4 Fetal Care Research Foundation, Chennai,
India.
MTHFR polymorphisms C677T and A1298C are reported to predispose
to neural tube defects (NTDs) in the western world. We studied
the association of these SNPs in 175 Indian women who carried fetuses
affected with NTDs and 332 unaffected fetuses (control). We
also measured maternal plasma folate, vitamin B12 and homocysteine
concentrations. Folate deficiency was observed only in 6% of mothers
who carried NTD fetuses. There was no association of maternal MTH-
FR SNPs with plasma folate, vitamin B12 or homocysteine concentrations
in cases, while in controls; TT genotype at C677T was associated
with significantly higher homocysteine concentrations.
Frequency of the risk allele T at the C677T polymorphism was 0.13 in
mothers with NTD fetuses and 0.14 in controls, while that of the risk
allele C at the A1298C polymorphism was 0.36 in mothers with NTD
fetuses and 0.47 in controls.
The 677T allele in mothers was not associated with NTDs in the offspring
(p=0.68) while the 1298C allele was more frequent in mothers
who had unaffected offspring (p=0.002). 1298C allele was noted to be
preferentially transmitted from mother to offspring in 75% of cases and
80% of controls, while 677T allele was preferentially transmitted from
mother to offspring in 60% of cases and 56% of controls. There was
no significant association between the above MTHFR polymorphisms
and NTDs in the offspring.
Our results suggest that the MTHFR polymorphisms which predispose
to NTDs in the western populations have limited contribution to the
etiology of NTDs in India.
P09.087
the common MTHFR c677t and A1298c variants are not
associated with the risk of non-syndromic cleft lip/palate in
northern Venezuela
M. A. Sözen 1,2 , M. M. Tolarova 3 , R. A. Spritz 2 ;
1 Afyon Kocatepe University School of Medicine, Afyonkarahisar, Turkey, 2 University
of Colorado Denver Human Medical Genetics Program, Aurora, CO,
United States, 3 University of the Pacific Department of Orthodontics, San Francisco,
CA, United States.
Non-syndromic cleft lip with/without palate (nsCL/P) is among the most
common of major birth defects, with a frequency of 1/500-1/2000 in
most populations and with complex inheritance probably involving multiple
genes and environmental factors. Numerous studies of MTHFR,
encoding methylenetetrahydrofolate reductase, which catalyzes the
rate-limiting step of folic acid biosynthesis, have yielded inconsistent
association of two common hypomorphic allelic variants, C677T and
A1298C. Some showed apparent allelic association between MTHFR
polymorphisms and nsCL/P in patients versus controls, and others
finding no or variable association. Other studies have reported association
in mothers of patients with nsCL/P. Also, contribution of mothers
genotype to the risk of nsCL/P has been reported. We have studied
the two common functionally significant MTHFR variants, C677T and
A1298C, in nsCL/P patients (n=179), their mothers (n=168), and population-matched
controls (n=138) from northern Venezuela. We found
no supporting evidence for contribution of both the MTHFR C677T and
A1298C polymorphisms to the risk of non-syndromic cleft lip with/without
palate in the population studied. Altogether, our data do not support
a causal role of either the MTHFR C677T or A1298C polymorphisms
in the pathogenesis of non-syndromic cleft lip with/without palate risk
in northern Venezuela.
P09.088
Influence of main, interaction and modified effects of NET,
ADRA2A and cOmt gene polymorphisms on personality traits in
healthy individuals
A. Kazantseva 1 , G. Faskhutdinova 1 , D. Gaysina 2 , E. Khusnutdinova 1 ;
1 Institute of Biochemistry and Genetics Ufa Scientific Center of Russian Academy
of Sciencies, Ufa, Russian Federation, 2 MRC Unit for Lifelong Health and