Association of common variants of CYP4A11 and CYP4F2 with stroke in the Han Chinese population.
Association of common variants of CYP4A11 and CYP4F2 with stroke in the Han Chinese population.
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DOI：
10.1097/fpc.0b013e328336eefe
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发表时间：
2010-03
影响因子：
2.6
通讯作者：
Wang DW
中科院分区：
文献类型：
--
作者：
Ding H;Cui G;Zhang L;Xu Y;Bao X;Tu Y;Wu B;Wang Q;Hui R;Wang W;Dackor RT;Kissling GE;Zeldin DC;Wang DW
20-羟基二十碳四烯酸（20-HETE）已被证明在脑血管功能中起重要作用。我们假设编码20-HETE合成酶的基因多态性可能赋予中风的易感性。为了验证这一假设，在558例缺血性脑卒中患者、221例出血性脑卒中患者和557例对照中对CYP 4A 11和CYP 4F 2基因的单倍型标记SNP（htSNPs）和潜在功能多态性进行了基因分型。在SNP和单倍型水平上进行关联分析。我们进一步验证了我们的研究结果在一个独立的队列551缺血性中风病例和48出血性中风受试者和694名未受影响的对照。我们发现CYP 4A 11 C-296 T和CYP 4F 2 V433 M与缺血性卒中风险显著增加相关（CT+TT vs CC，调整后比值比（OR）1.50，95%置信区间（CI）1.17-1.93，Pcombined=0.001，Pcorr=0.008; V/M+M/M vs. V/V，OR 1.38，95% CI，1.15-1.65，P合并=5.6×10−4，Pcorr=0.005）有趣的是，在我们的研究中，CYP 4F 2 V433 M对缺血性卒中的影响仅在男性受试者中明显。我们的研究结果表明，CYP 4A 11和CYP 4F 2的遗传变异改变了中国汉族人群对卒中的易感性。
20-Hydroxyeicosatetraenoic acid (20-HETE) has been shown to play an important role in cerebral vascular function. We hypothesized that polymorphisms in genes encoding 20-HETE synthesizing enzymes might confer susceptibility to stroke. To test the hypothesis, haplotype tagging SNPs (htSNPs) and potential functional polymorphisms of CYP4A11 and CYP4F2 genes were genotyped in 558 ischemic stroke patients, 221 hemorrhagic stroke patients and 557 controls. The association analyses were performed at both SNP and haplotype levels. We further verified our findings in an independent cohort of 551 ischemic stroke cases and 48 hemorrhagic stroke subjects and 694 unaffected controls. We identified CYP4A11 C-296T and CYP4F2 V433M were associated with significantly increased risk of ischemic stroke (CT+TT vs CC, adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.17–1.93, Pcombined=0.001, Pcorr=0.008; V/M+M/M vs. V/V, OR 1.38, 95% CI, 1.15–1.65, Pcombined=5.6×10−4, Pcorr=0.005, respectively) Interestingly, the effects of CYP4F2 V433M on ischemic stroke in our study was only evident in male subjects. Our results suggest that genetic variation in CYP4A11 and CYP4F2 alters susceptibility to stroke in the Han Chinese population.