Abstract
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.
Highlights
Reactive oxygen species (ROS) has been suggested to play a major role in vascular disease [1,2,3,4,5,6,7]
Khan et al provided no frequency of C242T polymorphism in cases and controls, and we failed to obtain these data by contacting the corresponding author, which limited our calculation of odds ratios (ORs) and 95% confidence intervals (95%confidence intervals (CIs)) for allelic model and additive model
It is well known that stroke is associated closely with conventional vascular risk factors [44] and genetic factors
Summary
Reactive oxygen species (ROS) has been suggested to play a major role in vascular disease [1,2,3,4,5,6,7]. The most significant sources of ROS in the vascular system are nicotinamide adenine dinucleotide phosphate (NADPH) oxidases [8], which include two membrane-bound subunits Nox and p22phox and the cytosolic components p47phox, p67phox, p40phox and Rac-1 [9,10]. Several polymorphisms of the CYBA gene have been reported, which could lead to significant functional variation among individuals in oxidative stress by influencing gene expression and NADPH oxidase activation [15,16,17]. Epidemiological 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 designed to clarify these controversies
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