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Associations of the NOS3 rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis
  1. Zhi Luo1,
  2. Aimei Jia2,
  3. Zhan Lu1,
  4. Irfan Muhammad1,
  5. Adebayo Adenrele3,
  6. Yongyan Song2
  1. 1 Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong city, Sichuan province, China
  2. 2 School of Preclinical Medicine, North Sichuan Medical College, Nanchong city, Sichuan province, China
  3. 3 Department of Anatomy, College of Veterinary Medicine, Federal University of Agriculture, Abeokuta, Nigeria
  1. Correspondence to Dr Yongyan Song, Biochemistry, North Sichuan Medical College, Nanchong, Sichuan 637008, China; songyongyan2014{at}


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 The association between the NOS3 rs1799983 polymorphism and CAD may be partly mediated by abnormal NO and lipid levels caused by the T allele.

  • nitric oxide synthase 3
  • nitric oxide
  • lipid
  • polymorphism
  • coronary artery disease

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  • Contributors YS and ZhiL conceived the study, participated in the design and drafted the manuscript. ZhiL, AJ, ZhanL, IM and AA carried out the study searches and collected the data. YS, ZhiL and ZhanL performed the statistical analyses.

  • Funding This project was supported by the Key Project of Education Department of Sichuan Province, People’s Republic of China (17ZA0172) and the Cooperative Project on Scientific Research between Nanchong city and North Sichuan Medical College, People’s Republic of China (NSMC20170403).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information.