Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Hum Immunol. 2011 Oct;72(10):921-5. doi: 10.1016/j.humimm.2011.07.309. Epub 2011 Aug 1.
Several whole-genome association studies have shown a significant link between childhood asthma and the 17q12 chromosome region. We selected tagging single nucleotide polymorphisms (SNPs) in the ORMDL3 gene (17q12) to investigate gene variability in relation to adult allergic asthma and asthma/atopy traits in a Czech Caucasian population of adults. We conducted a case-control association study comprising 668 unrelated subjects (337 asthmatic and 331 control subjects). Four selected SNPs (rs17608925, rs12603332, rs8076131, and rs3169572) were genotyped using the TaqMan SNP Genotyping Assays. The single locus analysis showed only a borderline association between rs3169572 variant and asthma (p = 0.030, p(corr) > 0.05). However, seven different haplotypes were identified; among them, the TTAA haplotype was marginally associated with asthma (p = 0.045, p(corr) > 0.05) and TCAG haplotype was significantly associated with asthma in males (p = 0.009, p(corr) < 0.05, odds ratio = 1.48, 95% confidence interval = 1.10-2.00). In addition, associations between the ORMDL3 genotypes and the total IgE level (p = 0.05, p(corr) > 0.05) and hypersensitivity to the pollen (p = 0.007, p(corr) < 0.05) were established. However, no relationship between ORMDL3 SNPs and the pulmonary functions was found (p > 0.05). These findings suggest that the genetic variability in the 17q21 region may be one of the risk factors also for adult asthma, especially in male individuals.
几项全基因组关联研究表明,儿童哮喘与 17q12 染色体区域之间存在显著关联。我们选择了 ORMDL3 基因(17q12)中的标签单核苷酸多态性(SNP),以调查捷克白种人群中与成人过敏性哮喘和哮喘/过敏特征相关的基因变异性。我们进行了一项病例对照关联研究,包括 668 名无关个体(337 名哮喘患者和 331 名对照者)。使用 TaqMan SNP 基因分型检测对 4 个选定的 SNP(rs17608925、rs12603332、rs8076131 和 rs3169572)进行了基因分型。单基因座分析显示,rs3169572 变异与哮喘之间只有边缘关联(p=0.030,p(corr)>0.05)。然而,鉴定出了 7 种不同的单倍型;其中,TTAA 单倍型与哮喘呈边缘关联(p=0.045,p(corr)>0.05),TCAG 单倍型与男性哮喘显著相关(p=0.009,p(corr)<0.05,优势比=1.48,95%置信区间=1.10-2.00)。此外,还发现 ORMDL3 基因型与总 IgE 水平(p=0.05,p(corr)>0.05)和花粉过敏(p=0.007,p(corr)<0.05)之间存在关联。然而,未发现 ORMDL3 SNP 与肺功能之间存在关系(p>0.05)。这些发现表明,17q21 区域的遗传变异性可能也是成人哮喘的危险因素之一,特别是在男性个体中。