The ALOXA5AP gene (rs38022789) is associated with diabetic nephropathy in Slovenian patients with type 2 diabetes mellitus

Gene. 2020 May 30:741:144551. doi: 10.1016/j.gene.2020.144551. Epub 2020 Mar 9.

Abstract

Background: Although the pathogenesis of diabetic nephropathy (DN) is multifactorial, and the precise mechanisms are unclear, there is a growing body of evidence suggesting that inflammatory processes and immune cells might be involved in the development and progression of DN. Leukotrienes (LTs) are a family of lipid mediators, which act as pro-inflammatory mediators. The study was designed to investigate the association between the polymorphism of the ALOX5 gene (rs12762303) and the ALOX5AP gene (rs3802278), and DN in patients with T2DM.

Methodology: 651 subjects with diabetes mellitus type 2 (T2DM) were classified into two groups according to the presence of DN, and tested for ALOX5 and ALOX5AP gene polymorphisms using the KASPar genotyping chemistry with validated assay. Biochemical analyses were performed using standard biochemical methods.

Results: Logistic regression analysis demonstrated that the carriers of the CC genotype had a 3.14 higher risk for DN compared to TT genotype. Serum cystatin C was found to be statistically significantly higher in cases with DN in comparison with subjects without DN (p < 0.001).

Conclusion: An association between the rs3803278 of the ALOX5AP gene and DN was found in Slovenian patients with T2DM. The rs3803278 CC allele appears to confer increased risk of DN possibly by increasing the production of LTs-potent drivers of inflammation.

Keywords: ALOX5; ALOX5AP; Diabetic nephropathy; Polymorphisms.

MeSH terms

  • 5-Lipoxygenase-Activating Proteins / genetics*
  • Adult
  • Alleles
  • Arachidonate 5-Lipoxygenase / genetics*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / pathology
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Substances

  • 5-Lipoxygenase-Activating Proteins
  • ALOX5AP protein, human
  • Arachidonate 5-Lipoxygenase
  • ALOX5 protein, human