诱导型一氧化氮合酶基因多态与脑卒中合并冠心病

A population-based study of the inducible nitric oxide synthase gene polymorphism for stroke with coronary artery disease in a Chinese population

目的 探讨诱导型一氧化氮合酶（NOS）2A基因多态与脑卒中合并冠心病发病的关系。方法 以ra28944190位点为遗传标记，采用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）检测708例脑卒中患者和235名对照组人群NOS2A基因的多态性。结果脑卒中组和对照组的rs28944190位点等位基因、基因型频率差异无统计学意义；以是否合并冠心病对病例组人群进行分层后，cocaphase分析表明合并冠心病的脑卒中组rs28944190位点的C等位基因频率（23．9％）较单纯脑卒中组（16．6％）明显增高（Х^2=5．629，P=0．018，DR=1．580，95％CI 1．083～2．306），这种差异在男性患者更加明显（Х^2=8．592，P=0．003，OR=1．983，95％CI 1．255～3．134）。卡方检验表明合并冠心病的脑卒中组Ac＋cc基因型的频率（47．9％）明显高于单纯脑卒中组（30．8％，Х^2=10．761,P=0．001，DR=2．065，95％CI 1．34～3．19），在男性患者差异更加明显（Х^2=15．762，P=0．000．OR=2．985,95％CI 1．74～5．12）。结论 NOS2A基因与脑卒中的发病可能无关，但可能与合并冠心病的脑卒中发病相关。

Objective To investigate the genetic association between the inducible nitric oxide synthase （NOS） 2A gene and stroke with a history of coronary artery disease （ CAD）. Methods 708 patients with stroke and 235 healthy controls were recruited in this study, and the stroke group was delaminated into 2 subgroups according to the history of CAD. SNP rs28944190, an A to C base change located in intron 22 of the gene, was used as a genetic marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs28944190 （HaeⅢ site）. Results The Х^2 test showed no association between patients with stroke and healthy controls. Of 708 patients, 94 had a history of CAD and the frequency of allele C of rs28944190 was significantly higher in patients with a history of CAD than those without （23.9% vs 16. 6%, Х^2 = 5.629, df= 1, P = 0. 018, OR = 1. 580, 95% CI 1. 083--2. 306）, especially in male patients （Х^2 = 8. 592, df = 1, P = 0. 003, OR = 1. 983, 95% CI 1. 255-3. 134 ）. The frequency of genotype AA ＋ AC of rs28944190 was significantly higher in patients with a history of CAD than those without such a history （47.9% vs 30. 8%, Х^2 = 10. 761, df= 1, P = O. 001, OR = 2.065, 95% CI 1.34-3.19）, especially in male patients （Х^2 = 15.762, df= 1, P =0. 000, OR =2. 985, 95% CI 1.74- 5.12）. Condusion The present study suggests that the NOS2A gene is unlikely to contribute to the etiology of stroke.