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

Kuroda J, Kitazono T, Ago T, Ninomiya T, Ooboshi H, Kamouchi M, Kumai Y, Hagiwara N, Yoshimura S, Tamaki K, Kusuda K, Fujii K, Nagao T, Okada Y, Toyoda K, Nakane H, Sugimori H, Yamashita Y, Wakugawa Y, Asano K, Tanizaki Y, Kiyohara Y, Ibayashi S, Iida M

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan.

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.

Published 20 September 2007 in Eur J Neurol, 14(10): 1091-7.
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