title: [Genome-wide association study of bronchial asthma in the Volga-Ural region of Russia].
abstract: Bronchial asthma is a chronic inflammatory respiratory disease that is caused by the complex interaction of environmental influences and genetic susceptibility. The first genome-wide association study of bronchial asthma discovered a significant association between SNPs within 17q12-21 genomic region and childhood bronchial asthma in individuals of European descent. Association with this genomic region was then replicated in a number of independent samples of European and Asian descent. Here we report results of the first genome-wide association study of bronchial asthma in the Volga-Ural region of Russia. The present study includes 358 unrelated patients with physician-diagnosed bronchial asthma and 369 disease-free control subjects of different ethnic origin (Russians, Tatars and Bashkirs). Genotyping of DNA samples was carried out using the Illumina Human610 quad array as a part of GABRIEL project (contract from the EC No LSHB-CT-2006-018996). After QC filtering procedures, a final set of 550915 SNPs genotyped in 330 cases and 348 controls was tested for association with bronchial asthma. Five markers on chromosome 17q12-21 showed statistically significant association with bronchial asthma (p < or = 4.79 x 10(-7)). SNP rs7216389 with the strongest evidence for association (p = 1.01 x 10(-7)) is located within the first intron of the GSDMB gene. Evidence for association was stronger with childhood-onset asthma (p = 1.97 x 10(-6) for SNP rs7216389) compared to late-onset asthma (p = 1.8 x 10(-4) for SNP rs7216389). Our replication study using three SNPs within GSDMB gene confirmed association with only childhood-onset asthma. In summary, these results suggest an important role for genetic variants within 17q12-q21 region in the development of bronchial asthma in the Volga-Ural region of Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Karunas
authors.forename: B B
authors.initials: BB
authors.lastname: Iunusbaev
authors.forename: Iu Iu
authors.initials: IuIu
authors.lastname: Fedorova
authors.forename: G F
authors.initials: GF
authors.lastname: Gimalova
authors.forename: N N
authors.initials: NN
authors.lastname: Ramazanova
authors.forename: L L
authors.initials: LL
authors.lastname: Gur'eva
authors.forename: L A
authors.initials: LA
authors.lastname: Mukhtarova
authors.forename: Sh Z
authors.initials: ShZ
authors.lastname: Zagidullin
authors.forename: E I
authors.initials: EI
authors.lastname: Etkina
authors.forename: E K
authors.initials: EK
authors.lastname: Khusnutdinova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004527:Egg Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012426:Russia; D000094524:Gasdermins
chemical_list: D004527:Egg Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C527978:GSDMB protein, human; D000094524:Gasdermins; C464399:ORMDL3 protein, human; C479482:ZPBP2 protein, human