Association of the C47T polymorphism in SOD2 with diabetes mellitus and diabetic microvascular complications: a meta-analysis

A meta-analysis was performed to assess the association of C47T (rs4880) (also called Val16Ala) polymorphism in SOD2 gene with reduced risk of diabetes mellitus, including type 1 and type 2 diabetes, and diabetic microvascular complications (DMI) including diabetic nephropathy, diabetic retinopathy and diabetic polyneuropathy. A comprehensive search was conducted to identify all case-control or cohort design studies of the above-mentioned associations. The fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. Heterogeneity among studies was evaluated using the I (2). Meta-regression and the 'leave one out' sensitive analysis of Patsopoulos et al. were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using modified Egger's linear regression test as proposed by Harbord et al. Seventeen articles were included. After excluding articles that deviated from Hardy-Weinberg equilibrium in cases and/or in controls, and were also the key contributors to between-study heterogeneity, the meta-analysis showed a significant association of the C allele with reduced risk of DMI in dominant (OR 0.788, 95% CI 0.680-0.914), recessive (OR 0.808, 95% CI 0.685-0.953) and codominant (OR 0.828, 95% CI 0.751-0.913) models. It also showed a significant association with reduced risk of diabetic nephropathy in the dominant model (OR 0.801, 95% CI 0.664-0.967), and reduced risk of diabetic retinopathy in the dominant (OR 0.601, 95% CI 0.423-0.855), recessive (OR 0.548, 95% CI 0.369-0.814) and codominant (OR 0.651, 95% CI 0.517-0.820) models. The meta-analysis suggested that C allele of C47T polymorphism in SOD2 gene has protective effects on risk of DMI, diabetic nephropathy and diabetic retinopathy. This risk needs to be confirmed by further studies.