NAD(P)H oxidase p22phox C242T polymorphism and ischemic stroke in Japan: the Fukuoka Stroke Registry and the Hisayama study

NAD(P)H oxidase p22phox C242T polymorphism and ischemic stroke in Japan: the Fukuoka Stroke Registry and the Hisayama study
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NAD(P)H 氧化酶 p22phox C242T 多态性与日本缺血性中风:福冈中风登记处和久山研究

DOI:
10.1111/j.1468-1331.2007.01904.x
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发表时间:
2007
影响因子:
5.1
通讯作者:
M. Iida
M. Iida
中科院分区:
医学3区
文献类型:
--
作者:
J. Kuroda;T. Kitazono;T. Ago;T. Ninomiya;H. Ooboshi;M. Kamouchi;Y. Kumai;N. Hagiwara;S. Yoshimura;K. Tamaki;K. Kusuda;K. Fujii;T. Nagao;Y. Okada;K. Toyoda;H. Nakane;H. Sugimori;Y. Yamashita;Y. Wakugawa;K. Asano;Y. Tanizaki;Y. Kiyohara;S. Ibayashi;M. Iida

文献摘要

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p22 phox基因C242 T多态性是NAD(P)H氧化酶的一个组成部分,可能对心血管疾病有影响;然而,该多态性与脑梗死之间的关系尚不完全清楚。在这里,我们调查了C242 T多态性与日本脑梗死之间的关系。我们招募了1055名脑梗死患者和1055名对照组。卡方检验显示,心源性梗死患者T等位基因频率(5.6%)低于对照组(11.0%,P  < 0.001);而腔隙性脑梗死和动脉粥样硬化性脑梗死患者的等位基因频率(11.2%)与对照组(11.0%)无显著性差异。多变量校正的条件logistic回归分析也显示CT + TT基因型与腔隙性和动脉粥样硬化血栓性梗死之间无相关性(比值比= 0.97,95%置信区间:0.72-1.32)。    为了研究C242 T多态性的功能效应,我们检测了每种基因型的Nox 4和p22 phox共转染的COS-7细胞中超氧化物的产生。在那些表达具有T等位基因的p22 phox的细胞中的超氧化物产生活性与表达具有C等位基因的p22 phox的细胞中的超氧化物产生活性没有显著差异。目前的研究结果表明,p22 phox C242 T多态性可能对心源性栓塞性梗死有保护作用,但与日本的腔隙性和动脉粥样硬化血栓性梗死无关。
The C242T polymorphism of p22phox, a component of NAD(P)H oxidase, may have an impact on cardiovascular diseases; however, the association between this polymorphism and brain infarction is not fully understood. Here, we investigate the relationship between the C242T polymorphism and brain infarction in Japan. We recruited 1055 patients with brain infarction and 1055 control subjects. A chi‐squared test revealed that the T‐allele frequency was lower in patients with cardioembolic infarction (5.6%) than in control subjects (11.0%, P < 0.001); however, allele frequencies in patients with lacunar and atherothrombotic infarction (11.2%) were not significantly different from those in control subjects (11.0%). A multivariate‐adjusted conditional logistic regression analysis also revealed no association between CT + TT genotype, and lacunar and atherothrombotic infarction (odds ratio = 0.97, 95% confidence interval: 0.72–1.32). To investigate the functional effects of the C242T polymorphism, we examined superoxide production in COS‐7 cells cotransfected with Nox4 and p22phox of each genotype. The superoxide‐producing activity in those cells expressing p22phox with the T allele was not significantly different from that in cells expressing p22phox with the C allele. The present results suggest that the p22phox C242T polymorphism may have a protective effect against cardioembolic infarction, but is not related to lacunar and atherothrombotic infarction in Japan.