2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
ethiopathology of MSD is largely unknown, but genetic disposition
may be one of several risk factors. Since pain is a major symptom of
MSD, and polymorphisms in the catecholamine O-Methyltransferase
(COMT) gene are associated with COMT enzymatic activity and pain
sensitivity, we assumed that COMT polymorphisms could be associated
with MSD.
Probands: 147 patients with MSD and 94 age and gender matched
healthy controls participated in this study. The inclusion criteria for
MSD were in accordance to the structured clinical interview (SCID) of
the diagnostic and statistical manual of mental disorders (DSM IV).
Genotyping: DNA from EDTA blood was genotyped for single nucleotide
polymorphisms (SNPs) within the COMT locus by polymerase
chain reaction (PCR) and restriction enzyme analysis. The distribution
of COMT SNP alleles, genotypes and haplotypes was compared between
patients and controls.
Results: None of the investigated SNPs, including the functionally relevant
common SNP in codon 158 (Val158Met), showed a statistically
significant allelic, genotypic or haplotypic association with MSD.
Discussion: In previous studies, convincing evidence was obtained for
a contribution of single SNPs and SNP haplotypes of the COMT locus
to differences in the human experience of pain and to the risk of developing
temporomandibular disorder (TMD). In contrast to these studies,
COMT polymorphisms do not seem to play a relevant role as major
genetic risk factors for MSD.
P09.011
Association analysis of xenobiotic-metabolizing gene
polymorphisms with asthma in Volga-Ural region of Russia
Y. Fedorova 1 , A. Karunas 1 , N. Ramazanova 2 , O. Gra 3 , I. Goldenkova-Pavlova 3 ,
E. Khusnutdinova 1 ;
1 Institute of Biochemistry and Genetics, Ufa, Russian Federation, 2 Bashkir
Medical State University, Ufa, Russian Federation, 3 Vavilov Institute of General
Genetics, Moscow, Russian Federation.
Asthma is a chronic inflammatory disorder of the airways in which
many cells and cellular elements play a role. The pathogenesis and
etiology of asthma are very complex. Some studies have shown an
association between asthma and polymorphisms of enzymes that
play an important role in the biotransformation of xenobiotics. Using
allele-specific hybridization on the biochip we have investigated the
allele and genotype distribution of 13 polymorphisms in eight genes
(CYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, NAT2, CYP2C9 and
CYP2C19). The study was performed in 264 patients with bronchial
asthma and 201 nonasthmatic individuals from Volga-Ural region of
Russia. Biochips were prepared in Engelhardt Institute of Molecular Biology,
Russian Academy of Sciences (Biochip-IMB, Russia). Significant
differences in NAT2 allele and genotype frequencies have been found
between asthma patients and control group of Russian ethnicity. The
frequency of slow *5/*5 genotype was lower in asthma patients than in
healthy subjects (OR=0,49; 95%CI 0,26-0,92; p=0,026). On the contrary
the Tatars had significant higher frequencies of *5 allele and *5/*5
genotype of NAT2 gene in patients than in control group (OR=1,54;
95%CI 1,01-2,35; p=0,045; OR=3,29; 95%CI 1,31-8,23; p=0,008). It is
known that polymorphic NAT2 status varies widely between individuals
and ethnic groups. Both rapid and slow N-acetyltransferase genotypes
have been associated with the risk of several diseases in a number
of populations. These observations, together with ethnic variation in
the ratio of slow and rapid acetylators, suggest that NAT2 genotypes
may partially explain asthma risk in different populations in Volga-Ural
region of Russia.
P09.012
ORmDL3 haplotype is associated with asthma in an italian
familial collection.
M. D. Bettin1 , G. Malerba1 , N. Klopp2 , E. Rodriguez2 , H. Grallert2 , N. Lindemann2
, L. Xumerle1 , R. Galavotti1 , C. Bombieri1 , E. Trabetti1 , T. Illig2 , P. F. Pignatti1
;
1Section of Biology and Genetics, Department of Mother and Child, Biology-Genetics,
Verona, Italy, 2Institute of Epidemiology, Helmholtz Zentrum München,
München, Germany.
Asthma is a complex disease with genetic and environmental components.
In 2007 the first Genome Wide Association study for asthma in English
and German subjects (Moffat MF, Nature 2007;448:470) reported a
strong association with 17q21 locus including the ORMDL3 gene. This
finding has been already replicated in different populations.
The association of 4 SNPs (rs8067378, rs7216389, rs3859192,
rs11650680) in the candidate locus with susceptibility to asthma was
investigated in Italian families with young asthmatic individuals (