Institute of Hypertension, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Acta Pharmacol Sin. 2011 Nov;32(11):1357-63. doi: 10.1038/aps.2011.114. Epub 2011 Oct 3.
To investigate the association of polymorphisms in four critical genes implicated in the NO-forming pathway with ischemic stroke (IS) in a Chinese Han population.
DNA samples of 558 IS patients and 557 healthy controls from Chinese Han population were genotyped using the Taqman(TM) 7900HT Sequence Detection System. Six SNPs (rs841, rs1049255, rs2297518, rs1799983, rs2020744, rs4673) of the 4 related genes (eNOS, iNOS, GCH1, and CYBA) in the NO forming pathway were analyzed using the SPSS 13.0 software package for Windows.
One SNP located in the intron of GCH1 (rs841) was associated with IS independent of the traditional cardiovascular risk factors in co-dominant and dominant models (P=0.003, q=0.027; P=0.00006, q=0.0108; respectively). Moreover, the combination of rs1049255 CC+CT and rs841 GA+AA genotypes was associated with significantly higher risk for IS after adjustments (OR=1.73, 95% CI: 1.27-2.35, P<0.0001, q<0.0001).
The data suggest that genetic variants within the NO-forming pathway alter susceptibility to IS in Chinese Han population. Replication of the present results in other independent cohorts is warranted.
在中国汉族人群中,研究与一氧化氮生成途径相关的四个关键基因中的多态性与缺血性脑卒中(IS)的相关性。
采用 Taqman(TM) 7900HT 序列检测系统对来自中国汉族人群的 558 例 IS 患者和 557 例健康对照者的 DNA 样本进行基因分型。对 4 个相关基因(eNOS、iNOS、GCH1 和 CYBA)中位于 NO 生成途径的 6 个 SNP(rs841、rs1049255、rs2297518、rs1799983、rs2020744 和 rs4673)进行分析。采用 SPSS 13.0 软件包进行 Windows 分析。
一个位于 GCH1 内含子中的 SNP(rs841)在共显性和显性模型中与传统心血管危险因素无关的 IS 相关(P=0.003,q=0.027;P=0.00006,q=0.0108;分别)。此外,rs1049255CC+CT 和 rs841GA+AA 基因型的组合在调整后与 IS 的发生风险显著增加相关(OR=1.73,95%CI:1.27-2.35,P<0.0001,q<0.0001)。
数据表明,NO 生成途径中的遗传变异改变了汉族人群 IS 的易感性。有必要在其他独立队列中复制本研究结果。