Yu X, Yu C, Ren Z, Deng Y, Song J, Zhang H, Zhou H
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, P. R. China; Department of Allergy, Harbin Children Hospital, Harbin, P. R. China.
Tissue Antigens. 2014 May;83(5):330-6. doi: 10.1111/tan.12342. Epub 2014 Mar 21.
A genome-wide association study (GWAS) suggested that variants on chromosome 17q21 were associated with childhood-onset asthma in white populations. Two replication studies had been conducted in southern Han Chinese population in 2009 and 2012. However, these two Chinese replication results were inconsistent. To further confirm the role of 17q21 common variants, an association study of 17q21 single nucleotide polymorphisms (SNPs) with the risk of childhood-onset asthma was performed in a Han population from northeastern China. In this study, rs3894194, rs12603332 and rs11650680 were genotyped in 435 asthmatic children and 601 healthy controls by using a SNaPshot method. Our data showed that the allelic frequency of rs12603332 and rs11650680 showed significant differences between asthmatic cases and healthy controls, with an odds ratio (OR) of 1.36 [95% confidence interval (CI) 1.12-1.65, P=0.002] and an OR of 1.36 (95% CI 1.07-1.74, P=0.01). Genotype distribution analysis also showed the significant associations of the above two loci with childhood asthma under dominant, recessive and additive model (dominant OR=1.57, 95% CI 1.04-2.36, P=0.032; recessive OR=1.41, 95% CI 1.09-1.83, P=0.009; additive OR=1.97, 95% CI 1.24-3.14, P=0.004; recessive OR=1.50, 95% CI 1.13-1.98, P=0.005). Besides, linear regression analysis showed that rs3894194 and rs12603332 were also significantly associated with asthma phenotypes such as log10 -transformed immunoglobulin E (IgE) level (IU/ml) and log10 -transformed eosinophil percentage (dominant, P=0.04; additive, P=0.01; recessive, P=0.04; recessive, P=0.03; additive, P=0.02). Collectively, our findings suggest that orosomucoid 1-like 3 (ORMDL3) locus on chromosome 17q21 is a risk factor for childhood-onset asthma in northeastern Han Chinese population. Further studies will be needed to elucidate the pathogenesis that ORMDL3 locus predisposes to childhood-onset asthma.
一项全基因组关联研究（GWAS）表明，17号染色体q21区域的变异与白种人群儿童期哮喘相关。2009年和2012年在南方汉族人群中进行了两项重复研究。然而，这两项中国重复研究的结果并不一致。为了进一步证实17q21常见变异的作用，在来自中国东北的汉族人群中进行了一项关于17q21单核苷酸多态性（SNP）与儿童期哮喘风险的关联研究。在本研究中，采用SNaPshot方法对435例哮喘儿童和601例健康对照进行了rs3894194、rs12603332和rs11650680基因分型。我们的数据显示，rs12603332和rs11650680的等位基因频率在哮喘病例和健康对照之间存在显著差异，优势比（OR）分别为1.36[95%置信区间（CI）1.12 - 1.65，P = 0.002]和1.36（95% CI 1.07 - 1.74，P = 0.01）。基因型分布分析还显示，在显性、隐性和加性模型下，上述两个位点与儿童哮喘存在显著关联（显性OR = 1.57，95% CI 1.04 - 2.36，P = 0.032；隐性OR = 1.41，95% CI 1.09 - 1.83，P = 0.009；加性OR = 1.97，95% CI 1.24 - 3.14，P = 0.004；隐性OR = 1.50，95% CI 1.13 - 1.98，P = 0.005）。此外，线性回归分析表明，rs3894194和rs12603332也与哮喘表型如log10转换的免疫球蛋白E（IgE）水平（IU/ml）和log10转换的嗜酸性粒细胞百分比显著相关（显性，P = 0.04；加性，P = 0.01；隐性，P = 0.04；隐性，P = 0.03；加性，P = 0.02）。总体而言，我们的研究结果表明，17号染色体q21区域的类正急性反应蛋白1样3（ORMDL3）基因座是中国东北汉族人群儿童期哮喘的一个危险因素。需要进一步研究来阐明ORMDL3基因座易患儿童期哮喘的发病机制。
