Association of endothelial nitric oxide synthase gene polymorphisms with type 2 diabetes mellitus: a meta-analysis

A meta-analysis was performed to assess the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms [4b4a VNTR and G894T (rs1799983)] with type 2 diabetes mellitus (T2DM). A comprehensive search was conducted to identify all eligible articles. Fixed or random effect pooled measure was selected based on homogeneity test. Heterogeneity among studies was evaluated using the I2. Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Egger's linear regression test. 19 articles involving 8,009 subjects for 4b4a VNTR and 19 articles involving 8,600 subjects for G894T were included. After excluding articles that deviated from Hardy-Weinberg equilibrium in controls and sensitivity analysis, significant association was found between 4a and increased risk of T2DM considering dominant model [OR (95% CI)=1.32 (1.17-1.48)], a vs. b [OR (95% CI)=1.34 (1.21-1.48)], and aa vs. bb [OR (95% CI)=1.52 (1.05-2.22)]. The 894T allele was also found associated with increased risk of T2DM considering dominant model [OR (95% CI)=1.14 (1.03-1.26)], recessive model [OR (95%CI)=1.28 (1.06-1.54)], T vs. G [OR (95% CI)=1.18 (1.09-1.27)], and TT vs. GG [OR (95% CI)=1.33 (1.09-1.62)]. The findings were consistent in Asian population. The meta-analysis indicated that NOS3 gene 4b4a VNTR and G894T polymorphisms might be associated with T2DM risk.