Anand Sonia S, Xie Changchun, Paré Guillaume, Montpetit Alexandre, Rangarajan Sumathy, McQueen Matthew J, Cordell Heather J, Keavney Bernard, Yusuf Salim, Hudson Thomas J, Engert James C
Population Health Research Institute, Hamilton Health Sciences, Ontario, Canada.
Circ Cardiovasc Genet. 2009 Feb;2(1):16-25. doi: 10.1161/CIRCGENETICS.108.813709. Epub 2009 Jan 23.
Myocardial infarction (MI) is a leading cause of death globally, but specific genetic variants that influence MI and MI risk factors have not been assessed on a global basis.
We included 8795 individuals of European, South Asian, Arab, Iranian, and Nepalese origin from the INTERHEART case-control study that genotyped 1536 single-nucleotide polymorphisms (SNPs) from 103 genes. One hundred and two SNPs were nominally associated with MI, but the statistical significance did not remain after adjustment for multiple testing. A subset of 940 SNPs from 69 genes were tested against MI risk factors. One hundred and sixty-three SNPs were nominally associated with a MI risk factor and 13 remained significant after adjusting for multiple testing. Of these 13, 11 were associated with apolipoprotein (Apo) B/A1 levels: 8 SNPs from 3 genes were associated with Apo B, and 3 cholesteryl ester transfer protein SNPs were associated with Apo A1. Seven of 8 of the SNPs associated with Apo B levels were nominally associated with MI (P<0.05), whereas none of the 3 cholesteryl ester transfer protein SNPs were associated with MI (P> or =0.17). Of the 3 SNPs most significantly associated with MI, rs7412, which defines the Apo E2 isoform, was associated with both a lower Apo B/A1 ratio (P=1.0x10(-7)) and lower MI risk (P=0.0004). Two low-density lipoprotein receptor variants, 1 intronic (rs6511720) and 1 in the 3' untranslated region (rs1433099) were both associated with a lower Apo B/A1 ratio (P<1.0x10(-5)) and a lower risk of MI (P=0.004 and P=0.003, respectively).
Thirteen common SNPs were associated with MI risk factors. Importantly, SNPs associated with Apo B levels were associated with MI, whereas SNPs associated with Apo A1 levels were not. The Apo E isoform, and 2 common low-density lipoprotein receptor variants (rs1433099 and rs6511720) influence MI risk in this multiethnic sample.
心肌梗死（MI）是全球主要的死亡原因之一，但尚未在全球范围内评估影响MI及MI危险因素的特定基因变异。
我们纳入了来自INTERHEART病例对照研究的8795名欧洲、南亚、阿拉伯、伊朗和尼泊尔裔个体，对103个基因的1536个单核苷酸多态性（SNP）进行基因分型。102个SNP与MI存在名义上的关联，但在多重检验校正后统计学意义不再显著。对来自69个基因的940个SNP子集针对MI危险因素进行检测。163个SNP与MI危险因素存在名义上的关联，在多重检验校正后13个仍具有显著性。在这13个SNP中，11个与载脂蛋白（Apo）B/A1水平相关：来自3个基因的8个SNP与Apo B相关，3个胆固醇酯转运蛋白SNP与Apo A1相关。与Apo B水平相关的8个SNP中有7个与MI存在名义上的关联（P<0.05），而3个胆固醇酯转运蛋白SNP均与MI无关联（P≥0.17）。在与MI最显著相关的3个SNP中，定义Apo E2异构体的rs7412与较低的Apo B/A1比值（P=1.0×10⁻⁷）和较低的MI风险（P=0.0004）均相关。两个低密度脂蛋白受体变异，1个在内含子区域（rs6511720），1个在3'非翻译区（rs1433099）均与较低的Apo B/A1比值（P<1.0×10⁻⁵）和较低的MI风险相关（分别为P=0.004和P=0.003）。
13个常见SNP与MI危险因素相关。重要的是，与Apo B水平相关的SNP与MI相关，而与Apo A1水平相关的SNP则不然。在这个多民族样本中，Apo E异构体以及2个常见的低密度脂蛋白受体变异（rs1433099和rs6
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