Apolipoprotein E genetic polymorphism influence the susceptibility to nephropathy in type 2 diabetes patients

Gene. 2019 Oct 5:715:144011. doi: 10.1016/j.gene.2019.144011. Epub 2019 Jul 26.

Abstract

Background: An association between Apolipoprotein E (Apo E) alleles and genotypes and diabetic nephropathy (DN) was suggested, but with inconsistent results. We tested the relationship between serum lipids, Apo E alleles and genotypes with type 2 diabetes (T2DM), and DN pathogenesis.

Methods: Study subjects comprised 1389 normoglycemic controls, and 1422 T2DM patients, of whom 825 were normoalbuminuric (DWN), and 597 presented with nephropathy (DN).

Results: Significantly lower Apo ε2, and higher Apo ε4 allele frequencies was seen among T2DM patients than controls. Significantly higher frequency of ε3/ε4, and lower frequencies of ε3/ε3, ε2/ε3, and ε4/ε4 carriers was seen among T2DM cases. Apo ε2-carrying individuals were more frequently found in controls than in patients, while significantly higher frequency of ε4-carrying genotypes was seen in T2DM cases. Significantly higher ε2, and lower ε3 allele frequencies were noted for DN group compared to DWN group. Significantly higher frequency of ε2-containing ε2/ε3 and ε2/ε4, and lower frequencies of ε3/ε3 carriers was seen among DN cases. Apo ε3/ε3 was associated with higher total cholesterol, LDL-cholesterol, and triglyceride levels in DN patients, and significantly higher triglyceride levels were seen in ε2/ε3-carrying DN patients. Logistic regression analysis confirmed the association of Apo ε3-containing ε3/ε3, ε2/ε3, and ε3/ε4, and Apo ε2-containing ε2/ε4 with DN, after controlling for key covariates.

Conclusion: The results of this case-control study provide evidence that the ε2 and ε3 alleles of APOE modify lipid profile, and constitute independent risk factors of DN in type 2 diabetes. The molecular mechanisms underlying this risk is discussed.

Keywords: Apolipoprotein E; Diabetic nephropathy; Genotyping; Type 2 diabetes mellitus.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Alleles*
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / genetics*
  • Female
  • Gene Frequency*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Risk Factors

Substances

  • Apolipoproteins E