Cysteinyl leukotriene receptor 1 gene variation and risk of asthma
Cysteinyl leukotriene receptor 1 gene variation and risk of asthma
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DOI：
10.1183/09031936.00057708
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发表时间：
2009-01-01
影响因子：
24.3
通讯作者：
Xu, X.
中科院分区：
文献类型：
--
作者：
Hong, X.;Zhou, H.;Xu, X.
虽然人们已经认识到遗传学在哮喘的发展中起着重要的作用，但重要的致病基因座仍有待确定。本研究的目的是检测已知和新的候选基因与哮喘的关联性，在中国同一地区招募了两个独立的样本，包括170例哮喘患者和347名对照的初始样本，以及202例哮喘患者和332名对照的确认样本。功能性单核苷酸多态性（SNPs;在初始样品中，三个SNP，半胱氨酰白三烯受体1基因中的rs 320995，肿瘤坏死因子受体超家族成员10 b中的rs-1047266，白细胞介素3基因中的rs 40401与哮喘的发病风险相关。值得注意的是，在隐性遗传模型下，SNP rs320995中没有胸苷等位基因的受试者患哮喘的风险高3.1倍，在考虑多次测试后仍然显着。这种关联在确认样本中得到了复制，并通过荟萃分析进行了验证。本研究为半胱氨酰白三烯受体1基因变异与哮喘发病风险相关提供了一致的证据。
Although it has been recognised that genetics plays an important role in the development of asthma, important causal loci remain to be identified. The aim of the present study was to examine the association of known and novel candidate genes with asthma.Two independent samples, including 170 asthmatic cases and 347 controls in the initial sample, and 202 asthmatic cases and 332 controls in the confirmation sample, were recruited from the same region of China. Functional single nucleotide polymorphisms (SNPs; n=129) from 105 genes were genotyped using MassARRAY technology, and 119 SNPs were used for the subsequent analysis.In the initial sample, three SNPs, rs320995 in the cysteinyl leukotriene receptor 1 gene, rs-1047266 in the tumour necrosis factor receptor superfamily, member 10b, gene and rs40401 in the interleukin-3 gene, were associated with risk of asthma. Notably, under the recessive genetic model, subjects without the thymidine allele in SNP rs320995 had a 3.1 times higher risk of asthma, which remained significant after accounting for multiple testing. This association was replicated in the confirmation sample and validated by meta-analysis. Further, sex-specific analysis was performed, but no sex difference was found.The present study provided coherent evidence that cysteinyl leukotriene receptor 1 gene variation is associated with risk of asthma.