Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.
PLoS Genet. 2011 Aug;7(8):e1002199. doi: 10.1371/journal.pgen.1002199. Epub 2011 Aug 4.
African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in European-Americans using a genome-wide association (GWAS) approach, no GWAS of incident CHD has been reported for African Americans. We performed a GWAS for incident CHD events collected during 19 years of follow-up in 2,905 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. We identified a genome-wide significant SNP (rs1859023, MAF = 31%) located at 7q21 near the PFTK1 gene (HR = 0.57, 95% CI 0.46 to 0.69, p = 1.86×10(-08)), which replicated in an independent sample of over 8,000 African American women from the Women's Health Initiative (WHI) (HR = 0.81, 95% CI 0.70 to 0.93, p = 0.005). PFTK1 encodes a serine/threonine-protein kinase, PFTAIRE-1, that acts as a cyclin-dependent kinase regulating cell cycle progression and cell proliferation. This is the first finding of incident CHD locus identified by GWAS in African Americans.
非裔美国人因冠心病（CHD）而死亡的比率最高。虽然已经使用全基因组关联（GWAS）方法在欧洲裔美国人中确定了多个影响 CHD 风险的基因座，但尚未有针对非裔美国人的 CHD 发病 GWAS 报道。我们对 2905 名来自社区动脉粥样硬化风险研究（ARIC）的非裔美国人进行了 19 年随访期间发生的 CHD 事件的 GWAS。我们在位于 PFTK1 基因附近的 7q21 处发现了一个与发病 CHD 相关的全基因组显著 SNP（rs1859023，MAF=31%）（HR=0.57，95%CI 0.46 至 0.69，p=1.86×10(-08)），该 SNP 在来自妇女健康倡议（WHI）的超过 8000 名非裔美国女性的独立样本中得到了复制（HR=0.81，95%CI 0.70 至 0.93，p=0.005）。PFTK1 编码丝氨酸/苏氨酸蛋白激酶 PFTAIRE-1，它作为一种细胞周期蛋白依赖性激酶，调节细胞周期进程和细胞增殖。这是非裔美国人首次通过 GWAS 发现的 CHD 发病相关基因座。
