Association between NADPH Oxidase p22phox C242T Polymorphism and Ischemic Cerebrovascular Disease: A Meta-Analysis

BackgroundEpidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies. Methodology/Principal FindingsSystematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93–1.26; additive model: OR = 1.33, 95%CI = 0.81–2.17; dominant model: OR = 1.00, 95%CI = 0.86–1.15; recessive model: OR = 1.06, 95%CI = 0.77–1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88–1.41; additive model: OR = 1.36, 95%CI = 0.60–3.09; dominant model: OR = 1.25, 95%CI = 0.74–2.11; recessive model: OR = 2.17, 95%CI = 1.11–4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%. Conclusions/SignificanceThis meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.背景 既往流行病学研究已探讨烟酰胺腺嘌呤二核苷酸磷酸（nicotinamide adenine dinucleotide phosphate, NADPH）氧化酶p22phox C242T多态性与缺血性脑血管病（ischemic cerebrovascular disease, ICVD）发病风险的关联，但研究结果尚存争议。本荟萃分析旨在厘清上述学术分歧。 方法与主要结果 系统检索Embase、PubMed、Web of Science等电子数据库，同时手工检索纳入文献的参考文献及相关会议摘要。采用Review Manager（版本5.1.7）与Stata（版本11.0）软件进行统计学分析。计算合并比值比（odds ratios, ORs）及其95%置信区间（95% confidence intervals, 95%CIs），根据研究间异质性分别选择固定效应模型或随机效应模型。采用Begg漏斗图与Egger回归检验评估发表偏倚。本研究共纳入6项相关研究，包含1948例病例与2357例对照。合并分析结果显示，NADPH氧化酶p22phox C242T多态性与总体缺血性脑血管病无统计学关联（等位基因模型：OR=1.08，95%CI=0.93–1.26；加性模型：OR=1.33，95%CI=0.81–2.17；显性模型：OR=1.00，95%CI=0.86–1.15；隐性模型：OR=1.06，95%CI=0.77–1.45）。在大动脉粥样硬化性卒中亚组中发现显著关联（等位基因模型：OR=1.12，95%CI=0.88–1.41；加性模型：OR=1.36，95%CI=0.60–3.09；显性模型：OR=1.25，95%CI=0.74–2.11；隐性模型：OR=2.17，95%CI=1.11–4.23）。而在小血管闭塞性卒中亚组、亚洲人群亚组及高加索人群亚组中，未观察到统计学意义的关联。所有合并样本（总体及亚组）的统计效力均低于80%。 结论与意义 本荟萃分析结果表明，相较于小血管闭塞性卒中，NADPH氧化酶p22phox C242T多态性与大动脉粥样硬化性卒中的关联更为显著。但由于样本量较小，对该结论的解读需谨慎。未来仍需开展样本量更大、缺血性脑血管病患者队列更同质且对照匹配更严谨的相关研究。