Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population
Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population
复制标题
中国汉族人群候选基因关联研究中ITGA2、PON1和THBS2常见多态性与冠状动脉粥样硬化相关
DOI：
10.1038/jhg.2010.53
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发表时间：
2010-08-01
影响因子：
3.5
通讯作者：
Huang, Wei
中科院分区：
文献类型：
--
作者：
Wang, Ying;Fu, Wenqing;Huang, Wei
冠状动脉粥样硬化是一种复杂的进行性疾病，涉及许多生物学途径，包括氧化应激和炎症反应途径。为了研究这两个通路中常见的遗传变异与冠状动脉粥样硬化之间的关联，我们在中国汉族人群中进行了一项全面的两阶段候选基因关联研究。在第I阶段，对293例冠状动脉粥样硬化患者和293名年龄和性别匹配的健康对照者的116个候选基因中的936个标签单核苷酸多态性（SNP）进行基因分型。在第二阶段，从第一阶段选择了51个SNP，并在另外1030例病例和764例对照中进一步进行基因分型。在II期的基于等位基因和基因型的关联性检验和两个阶段的荟萃分析中，我们在三个基因中鉴定了三个SNP，即ITGA 2中的rs3212556，（P CMH= 9.20× 10− 5），PON1中的rs854563（P CMH= 1.92× 10− 4）和THBS2中的rs9283851（P CMH= 3.00× 10− 3）。单倍型分析为rs3212556（P global< 10− 4）和rs854563（P global< 10− 4）的关联提供了进一步的支持证据。我们的研究已经确定了ITGA 2，PON1和THBS2内的三个SNP与冠状动脉粥样硬化相关。
Coronary atherosclerosis is a complex and progressive condition that involves many biological pathways, including the oxidative stress and inflammatory response pathways. To investigate the association between common genetic variation within these two pathways and coronary atherosclerosis, we performed a comprehensive two-stage candidate gene association study in a Chinese Han population. In stage I, 936 tag single-nucleotide polymorphisms (SNPs) within 116 candidate genes were genotyped in 293 coronary atherosclerosis cases and 293 age-and gender-matched healthy controls. In stage II, 51 SNPs from stage I were selected and further genotyped in an additional 1030 cases and 764 controls. In allele-and genotype-based association tests of stage II and a meta-analysis across the two stages, we identified three SNPs within three genes significantly associated with the disease, namely rs3212556 in ITGA2 (P CMH= 9.20× 10− 5), rs854563 in PON1 (P CMH= 1.92× 10− 4) and rs9283851 in THBS2 (P CMH= 3.00× 10− 3). Haplotype analysis provided further supporting evidence for the association of rs3212556 (P global< 10− 4) and rs854563 (P global< 10− 4). Our study has identified three SNPs within ITGA2, PON1 and THBS2 that are associated with coronary atherosclerosis.