A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction
A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction
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DOI：
10.1007/s10038-006-0102-5
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发表时间：
2007-03-01
影响因子：
3.5
通讯作者：
Tanaka, Toshihiro
中科院分区：
文献类型：
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作者：
Ebana, Yusuke;Ozaki, Kouichi;Tanaka, Toshihiro
心肌梗死 (MI) 是多种遗传和环境因素复杂相互作用的结果。为了揭示 MI 的遗传背景，我们使用 52,608 个基于基因的单核苷酸多态性 (SNP) 标记进行了大规模病例对照关联研究，并鉴定了位于染色体 3p21.2-p21.1 上的候选 SNP。随后的连锁不平衡图谱表明，MI 与 inter-α（球蛋白）抑制剂 3 基因外显子 2 中的 SNP 之间存在非常显着的关联（ITIH3；chi(2) = 24.88，P = 6.1 x 10(-7)，3,353 名受影响个体与 3,807 名对照个体）。体外功能分析表明该SNP增强了ITIH3基因的转录水平。此外，我们发现ITIH3蛋白在人类动脉粥样硬化病变的血管平滑肌细胞和巨噬细胞中表达，表明ITIH3 SNP是MI的一个新的遗传危险因素。
Myocardial infarction (MI) results from complex interactions of multiple genetic and environmental factors. To disclose genetic backgrounds of MI, we performed a large-scale, case-control association study using 52,608 gene-based single-nucleotide polymorphism (SNP) markers, and identified a candidate SNP located on chromosome 3p21.2-p21.1. Subsequent linkage-disequilibrium mapping indicated very significant association between MI and a SNP in exon 2 of the inter-alpha (globulin) inhibitor 3 gene (ITIH3; chi(2) = 24.88, P = 6.1 x 10(-7), 3,353 affected individuals versus 3,807 controls). In vitro functional analyses showed that this SNP enhanced the transcriptional level of the ITIH3 gene. Furthermore, we found expression of the ITIH3 protein in the vascular smooth muscle cells and macrophages in the human atherosclerotic lesions, suggesting ITIH3 SNP to be a novel genetic risk factor of MI.