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NOS1AP 基因上的 rs12143842 遗传变异增加了汉族人群特发性室性心动过速的风险。

The genetic variation rs12143842 in NOS1AP increases idiopathic ventricular tachycardia risk in Chinese Han populations.

机构信息

First Affiliated Hospital of Dalian Medical University, Dalian, China.

出版信息

Sci Rep. 2017 Aug 21;7(1):8356. doi: 10.1038/s41598-017-08548-z.

Abstract

Genome-wide association studies identified that the common T of rs12143842 in NOS1AP is associated with a QT/QTc interval in European populations. In this study, we test the association between the variation rs12143842 in NOS1AP and idiopathic ventricular tachycardia (IVT). A case-control association study examining rs12143842 was performed in two independent cohorts. The Northern cohort enrolled 277 IVT patients and 728 controls from a Chinese Gene ID population. The Central cohort enrolled 301 IVT patients and 803 matched controls. Genotyping was performed using high-resolution melt analysis. The minor T allele of the rs12143842 SNP was significantly associated with decreased IVT risk in the Northern cohort (adjusted P = 0.024, OR 0.71(0.520.96)), and this association was replicated in an independent Central Gene ID cohort (adjusted P = 0.029, OR 0.78 (0.620.97)). The association was more significant in the combined population (adjusted P = 0.001, OR 0.76 (0.64~0.90)). The P values for the genotypic association were significant for the dominant (P < 0.001) and additive (P = 0.001) models. The minor T allele for the SNP rs12143842 in NOS1AP is significantly associated with IVT. NOS1AP might be a novel gene affecting IVT, and further functional studies should be performed.

摘要

全基因组关联研究表明,NOS1AP 基因上 rs12143842 的常见 T 等位基因与欧洲人群的 QT/QTc 间期有关。在这项研究中,我们检验了 NOS1AP 基因中的变异 rs12143842 与特发性室性心动过速(IVT)之间的关联。我们在两个独立的队列中进行了 NOS1AP 基因 rs12143842 变异的病例对照关联研究。北方队列纳入了来自中国基因 ID 人群的 277 例 IVT 患者和 728 例对照。中央队列纳入了 301 例 IVT 患者和 803 例匹配对照。采用高分辨率熔解分析进行基因分型。rs12143842 单核苷酸多态性的次要 T 等位基因与北方队列中 IVT 风险降低显著相关(调整后的 P=0.024,OR 0.71(0.520.96)),这种关联在独立的中央基因 ID 队列中得到了复制(调整后的 P=0.029,OR 0.78(0.620.97))。在合并人群中,这种关联更为显著(调整后的 P=0.001,OR 0.76(0.64~0.90))。对于显性(P<0.001)和加性(P=0.001)模型,基因型关联的 P 值均具有统计学意义。NOS1AP 基因 rs12143842 中的 SNP 次要 T 等位基因与 IVT 显著相关。NOS1AP 可能是一个影响 IVT 的新基因,应该进行进一步的功能研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a71f/5567283/3b44dd766999/41598_2017_8548_Fig1_HTML.jpg

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