The A930G Polymorphism of P22phox (CYBA) Gene but Not C242T Variation Is Associated with Hypertension: A Meta-Analysis

Abstract

BackgroundRecently, it has been reported that the A930G and C242T polymorphisms within p22phox (CYBA) gene are involved in the pathogenesis of hypertension. However, the results remain controversial. Furthermore, no previous meta-analysis has been conducted to evaluate the relationship between the A930G and C242T polymorphisms and hypertension. Therefore, we performed this meta-analysis to clarify these controversies.Objective and MethodsAll of the included articles were retrieved from the PubMed and Embase databases, as well as the CNKI, CBM, Chongqing VIP and Wan Fang databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were used to assess the strength of the association. Accounting for heterogeneity, a fixed or random effects model was respectively adopted. Heterogeneity was checked using the Q test and the I2 statistic. A cumulative meta-analysis was conducted to estimate the tendency of pooled OR. Funnel plots and Egger’s tests were performed to test for possible publication bias.ResultsFive articles on A930G with 2003 cases/2434 controls and eight articles on C242T with 2644 cases/1967 controls were identified. A significant association of A930G polymorphisms with the risk of hypertension was found in the dominant model (OR=0.59, 95% CI: 0.38–0.92, p=0.021) and allelic model (OR=0.66, 95% CI: 0.46–0.95, p=0.024). In the stratified analysis, a significant association could be found among the hospital-based and population-based studies. However, no evidence of a significant association of the C242T polymorphism with hypertension was found in the overall analysis and subgroup analysis.ConclusionsThis meta-analysis indicates that the A930G polymorphism, but not the C242T variation, might be a protective factor for hypertension.

Association between the nicotinamide adenine dinucleotide phosphate oxidase p22phox gene -A930G polymorphism and intracerebral hemorrhage

“…It has been observed that the -A930G polymorphism is associated with hypertension. Hypertensive patients with a GG genotype exhibit increased p22phox mRNA and protein levels and enhanced NAD(P)H oxidase activity compared with those with an AA or AG genotype, while no difference is observed in these parameters in healthy subjects (13).…”

“…There is accumulating evidence that the -A930G polymorphism of the p22phox subunit of NAD(P)H oxidases is associated with ICH (13). Membrane-associated NAD(P)H oxidases are the main enzymes responsible for ROS generation in neutrophil granulocytes and the vasculature, which may be important in the pathogenesis of ischemic injury and atherosclerosis (14).…”

“…The gene encoding the p22phox subunit, CYBA, is located on the long arm of chromosome 16 (16q24), spans a length of 8.5 kb and contains six exons and five introns (16). The -A930G polymorphism is located at the promoter region and the G allele has increased promoter activity and a higher level of ROS, leading to increased vascular smooth muscle cell proliferation, endothelial dysfunction and the formation of lesions, which can contribute to cerebrovascular disease (13). It has been observed that the -A930G polymorphism is associated with hypertension.…”

CYBA encoding p22phox, the cytochrome b558 alpha polypeptide: gene structure, expression, role and physiopathology

“…Finally, beginning in 2010 nine Chinese meta-analyses of the C242T polymorphism were published in relation with coronary artery disease (CAD) (Fang et al, 2010; Wu et al, 2013; Liang et al, 2014; Xu et al, 2014b; Hu et al, 2015), hypertension (Qin et al, 2013), atherosclerosis or diabetes and its complications (Li et al, 2015) and ischemic cerebrovascular diseases (Gu et al, 2013; Li et al, 2013). Three of them were associated with the analysis of A930G or A640G polymorphisms (Qin et al, 2013; Liang et al, 2014; Xu et al, 2014b).…”

“…Three of them were associated with the analysis of A930G or A640G polymorphisms (Qin et al, 2013; Liang et al, 2014; Xu et al, 2014b). The results of these meta-analyses are summarized in Table 3.…”