Karunas A S, Iunusbaev B B, Fedorova Iu Iu, Gimalova G F, Ramazanova N N, Gur'eva L L, Mukhtarova L A, Zagidullin Sh Z, Etkina E I, Khusnutdinova E K
Mol Biol (Mosk). 2011 Nov-Dec;45(6):992-1003.
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.
支气管哮喘是一种慢性炎症性呼吸系统疾病,由环境影响和遗传易感性的复杂相互作用引起。第一项全基因组关联研究发现,在欧洲血统个体中,17q12 - 21基因组区域内的单核苷酸多态性(SNP)与儿童支气管哮喘之间存在显著关联。随后,在多个欧洲和亚洲血统的独立样本中重复发现了与该基因组区域的关联。在此,我们报告俄罗斯伏尔加 - 乌拉尔地区第一项支气管哮喘全基因组关联研究的结果。本研究纳入了358名经医生诊断为支气管哮喘的无亲缘关系患者以及369名不同种族(俄罗斯人、鞑靼人和巴什基尔人)的无病对照受试者。作为GABRIEL项目(来自欧盟委员会的合同编号LSHB - CT - 2006 - 018996)的一部分,使用Illumina Human610 quad阵列对DNA样本进行基因分型。经过质量控制过滤程序后,对在330例病例和348例对照中基因分型的550915个SNP的最终集合进行了与支气管哮喘的关联性测试。17号染色体q12 - 21上的五个标记与支气管哮喘显示出统计学上的显著关联(p≤4.79×l0⁻⁷)。关联证据最强的SNP rs7216389(p = 1.01×l0⁻⁷)位于GSDMB基因的第一个内含子内。与迟发性哮喘相比,儿童期发病哮喘的关联证据更强(SNP rs7216389的p = 1.97×l0⁻⁶)(SNP rs7216389的p = 1.8×l0⁻⁴)。我们使用GSDMB基因内的三个SNP进行的重复研究证实,仅与儿童期发病哮喘存在关联。总之,这些结果表明17q12 - q21区域内的遗传变异在俄罗斯伏尔加 - 乌拉尔地区支气管哮喘的发病中起重要作用。