Association of extracellular superoxide dismutase Ala40Thr, Arg213Gly, and Leu53Leu polymorphisms with risk of type 2 diabetes mellitus in a Chinese population

Objective: We performed a study to investigate the association of EC-SOD Ala40Thr (rs2536512), Arg213Gly (rs8192291) and Leu53Leu (rs1799895) polymorphisms and haplotypes with the risk of T2DM, and their correlation with environmental factors. Methods: A total of 612 Chinese patients with T2DM and 630 healthy volunteers were enrolled in our study between Jun 2013 and Jun 2015. An iPlex GLOD SNP genotyping analysis of EC-SOD Ala40Thr (rs2536512), Arg213Gly (rs8192291) and Leu53Leu (rs1799895) was run in a 384 well plate format using the Sequenom MassARRAY® System. Results: The CT (OR=1.46, 95% CI=1.13-1.90) and TT (OR=1.92, 95% CI=1.30-2.84) genotype were associated with a moderate increased risk of T2DM, in comparison to the CC genotype. The CT+TT genotype also displayed an elevated risk of T2DM when compared with the CC genotype (OR=1.44, 95% CI=1.14-1.80). The TT+CT genotype was correlated with risk of T2DM in those with older age (OR=1.59, 95% CI=1.19-2.14), never drinkers (OR=1.82, 95% CI=1.25-2.63), a family history of T2DM (OR=1.44, 95% CI=1.14-1.82) and a higher BMI (OR=1.56, 95% CI=1.13-2.17). The G-C-C and G-C-G haplotypes were associated with a reduced risk of T2DM, while the G-T-C haplotype was correlated with an increased risk. Conclusion: The EC-SOD Arg213Gly (rs8192291) polymorphism is correlated with an increased risk of T2DM, especially in males, never drinkers, those with a family history of T2DM and overweight subjects. The G-C-C, G-C-G and G-T-C contribute to the pathogenesis of T2DM.