Key result
The NOS type III 4b/a polymorphism was significantly associated with increased susceptibility to diabetic nephropathy compared with diabetes patients globally (OR 1.26; 95% CI 1.10-1.45).
Why the study?
Is the NOS type III 4b/a polymorphism associated with an increased risk of diabetic nephropathy?
Meta-Analysis (n=15,526)
Is the NOS type III 4b/a polymorphism associated with an increased risk of diabetic nephropathy?
Odds Ratio: 1.26 (95% CI 1.1–1.45)
The NOS type III 4b/a polymorphism is associated with an increased risk of developing diabetic nephropathy, particularly in Asian populations and type 2 diabetes patients.
Confirms global association of NOS type III 4b/a with diabetic nephropathy risk; leaves open utility for genetic risk stratification.
To clarify the effect of nitric oxide synthase (NOS) type III 4b/a polymorphism on the susceptibility to diabetic nephropathy (DN) by meta-analysis, we performed a computerized search of PubMed, EMBASE, Chinese BioMedical Literature Database, China Science and Technology Journal Database, Chinese Journal Full-text Database and WanFang to identity case-control studies on relationship between NOS type III 4b/a polymorphism and the susceptibility to DN. Statistic analysis and heterogeneity test were conducted by StataSE12. The meta-analysis involved 26 studies for DN comparing with diabetes mellitus (DM) and 15 studies for DN comparing with healthy persons, which provided 6144/4900 cases/controls and 2134/2348 cases/controls, respectively. Moderate heterogeneity was found among including studies. The qualities of half studies are low. Meta-analysis derived a significant association between the NOS type III 4b/a and the risk of developing DN in Asian population. The sensitivity analysis (exclusion of studies not in Hardy-Weinberg equilibrium) produced non-significant changes. Compared with diabetes patients, the pre-allele model produced certain association in global populations [odds ratio (OR) = 1.26, 95% confidence interval (95% CI): 1.10-1.45], significant association in Asian population (OR = 1.51, 95% CI: 1.13-2.01) and certain association in type 2 DM patients (OR = 1.29, 95% CI: 1.09-1.54). Only in the dominant model, the funnel plot and Egger's test provided evidence of publication bias (p = 0.024). Overall, although there is some evidence of association between NOS type III 4b/a polymorphism and DN in Asian population, the more reliable findings need further and more rigorous, prospective and high-quality studies.
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Zeng et al. (2014) conducted a meta-analysis in Diabetic nephropathy (n=15,526). NOS type III 4b/a polymorphism vs. Diabetes mellitus patients or healthy persons was evaluated on Susceptibility to diabetic nephropathy (OR 1.26, 95% CI 1.10-1.45). The NOS type III 4b/a polymorphism was significantly associated with increased susceptibility to diabetic nephropathy compared with diabetes patients globally (OR 1.26; 95% CI 1.10-1.45).
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