Abstract
BackgroundSeveral epidemiological studies have evaluated the association between the NAD(P)H oxidase p22 phox gene C242T polymorphism and the risk of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and carotid atherosclerosis with T2DM (CA), but the results are inconclusive. This meta-analysis was therefore designed to clarify these controversies. MethodsSystematic searches were performed using electronic databases such as MEDLINE, PubMed, EMBASE, and China National Knowledge Infrastructure, as well as through manual searching of the references of identified articles. A total of 11 publications were eligible for this meta-analysis after running a search on the NAD(P)H oxidase p22 phox gene C242T polymorphism, including 7 with outcomes for T2DM, 7 with outcomes for DN, and 3 with outcomes for CA. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using a fixed effects model (FEM) or a random effects model (REM). Publication bias was tested by Begg's funnel plot analysis. Sensitivity analysis was also performed. ResultsThe results showed a significant association between the NAD(P)H oxidase p22 phox gene C242T polymorphism and T2DM risk in the allelic model (REM: OR=1.23, 95% CI=1.06–1.43), additive model (FEM: OR=1.61, 95% CI=1.14–2.26), and recessive model (FEM: OR=1.50, 95% CI=1.10–2.05). A significant association was also observed for DN in the allelic model (REM: OR=1.25, 95% CI=1.06–1.47), additive model (FEM: OR=1.61, 95% CI=1.08–2.38), and dominant model (REM: OR=1.26, 95% CI=1.03–1.54). However, no association was observed for CA. Similar results were obtained in subgroup analysis based on ethnicity. ConclusionsResults of this meta-analysis suggest that the NAD(P)H oxidase p22 phox gene 242T allele might be associated with an increased risk of T2DM and DN, but not CA.
Highlights
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, causing significant morbidity and mortality worldwide (Gulliford and Charlton, 2009)
We retrieved the full text for the remaining 25 articles for further evaluation using the inclusion criteria, and a total of 11 publications were found eligible for this meta-analysis (Doi et al 2005; Hayaishi-Okano et al 2003; Jin et al, 2011; Letonja et al 2012; Lim et al 2006; Liu et al, 2006; Matsunaga-Irie et al 2004; Narne et al 2014; Santos et al, 2005; Yan, 2005; Yang et al, 2006), including 7 with outcomes for type 2 diabetes mellitus (T2DM), 7 with outcomes for diabetic nephropathy (DN), and 3 with outcomes for carotid atherosclerosis with T2DM (CA) resulting from a search on the NAD(P)H oxidase p22 phox gene C242T polymorphism (Fig. 1)
We found that the odds ratio (OR) and 95% confidence interval (CI) were materially altered by limiting the meta-analysis to studies conforming to the Hardy–Weinberg equilibrium (HWE) or those with outlier OR values, and the risk effects of the T allele were no longer significant
Summary
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, causing significant morbidity and mortality worldwide (Gulliford and Charlton, 2009). Several epidemiological studies have evaluated the association between the NAD(P)H oxidase p22 phox gene C242T polymorphism and the risk of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and carotid atherosclerosis with T2DM (CA), but the results are inconclusive. This meta-analysis was designed to clarify these controversies. Conclusions: Results of this meta-analysis suggest that the NAD(P)H oxidase p22 phox gene 242T allele might be associated with an increased risk of T2DM and DN, but not CA
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