Associations of theNOS3rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis

BACKGROUND: Circulating nitric oxide (NO) and lipid levels are closely associated with coronary artery disease (CAD). It is unclear whether the rs1799983 polymorphism in endothelial nitric oxide synthase (NOS3) gene is associated with plasma levels of NO and lipids. This systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) aimed to clarify the relationships between the rs1799983 polymorphism and plasma levels of NO and lipids. METHODS: Sixteen studies (2702 subjects) and 59 studies (14 148 subjects) were identified for the association analyses for NO and lipids, respectively. Mean difference (MD) and 95% CI were used to estimate the effects of the rs1799983 polymorphism on plasma NO and lipid levels. The primary outcome variable was NO, and the secondary outcomes included triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). RESULTS: Carriers of the T allele had lower levels of NO (MD -0.27 μmol/L, 95% CI -0.42 to -0.12 μmol/L, p<0.001) and HDL-C (MD -0.07 mmol/L, 95% CI -0.14 to -0.00 mmol/L, p=0.04), and higher levels of TC (MD 0.13 mmol/L, 95% CI 0.06 to 0.20 mmol/L, p<0.001) and LDL-C (MD 0.14 mmol/L, 95% CI 0.05 to 0.22 mmol/L, p=0.002) than the non-carriers. Triglyceride levels were comparable between the genotypes. CONCLUSION: rs1799983 polymorphism and CAD may be partly mediated by abnormal NO and lipid levels caused by the T allele.