The Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with the Susceptibility to Immunoglobulin a Nephropathy in Chinese Population

Kidney Blood Press Res. 2017;42(3):608-616. doi: 10.1159/000481421. Epub 2017 Sep 25.

Abstract

Background/aims: Endothelial nitric oxide synthase (eNOS) is one of the most important enzymes for producting nitric oxide (NO), which regulate the function of many organs and cells. The single nucleotide polymorphisms (SNPs) of eNOS were found to be associated with many kidney diseases. However, it is lack of relevant studies to evaluate the associations between eNOS polymorphisms and immunoglobulin A nephropathy (IgAN). This case-control study aimed to evaluate the relationship between eNOS polymorphisms and IgAN.

Methods: We recruited 351 IgAN patients and 310 age- and sex-matched healthy controls from Northwest China. Sequenom MassARRAY was used to detect the genotypes of two common eNOS SNPs (rs1799983 and rs2070744). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between eNOS and IgAN. Phase 2.1 was used to conduct haplotype analysis.

Results: In the overall analysis, we found that the rs1799983 polymorphism was associated with a decreased risk of IgAN (G/T vs. G/G: OR=0.57, 95%CI=0.34-0.96; G/T+T/T vs. G/G: OR=0.52, 95%CI=0.31-0.86; G/T vs.

G/g-t/t: OR=0.60, 95%CI=0.36-0.99; Log-additive model: OR=0.48, 95%CI=0.30-0.78). Haplotype analysis indicated that Trs1799983Crs2070744 is a protective factor against IgAN (OR=0.62, 95%CI=0.42--0.92). However, no significant differences were found between the two SNPs (rs1799983 and rs2070744) and clinical features (age, sex, blood pressure, and Lee's grade) of IgAN.

Conclusion: The eNOS gene rs1799983 polymorphism and Trs1799983Crs2070744 haplotype may reduce the risk of IgAN in Chinese populations.

Keywords: Endothelial nitric oxide synthase; IgA nephropathy; Risk; Rs1799983; Rs2070744; Single-nucleotide polymorphisms.

MeSH terms

  • Adult
  • Asian People / genetics
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Glomerulonephritis, IGA / genetics*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Single Nucleotide*
  • Young Adult

Substances

  • NOS3 protein, human
  • Nitric Oxide Synthase Type III