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

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 epsilon 2, and higher Apo epsilon 4 allele frequencies was seen among T2DM patients than controls. Significantly higher frequency of epsilon 3/epsilon 4, and lower frequencies of epsilon 3/epsilon 3, epsilon 2/epsilon 3, and epsilon 4/epsilon 4 carriers was seen among T2DM cases. Apo epsilon 2-carrying individuals were more frequently found in controls than in patients, while significantly higher frequency of epsilon 4-carrying genotypes was seen in T2DM cases. Significantly higher epsilon 2, and lower epsilon 3 allele frequencies were noted for DN group compared to DWN group. Significantly higher frequency of epsilon 2-containing epsilon 2/epsilon 3 and epsilon 2/epsilon 4, and lower frequencies of epsilon 3/epsilon 3 carriers was seen among DN cases. Apo epsilon 3/epsilon 3 was associated with higher total cholesterol, LDL-cholesterol, and triglyceride levels in DN patients, and significantly higher triglyceride levels were seen in epsilon 2/epsilon 3-carrying DN patients. Logistic regression analysis confirmed the association of Apo epsilon 3-containing epsilon 3/epsilon 3, epsilon 2/epsilon 3, and epsilon 3/epsilon 4, and Apo epsilon 2-containing epsilon 2/epsilon 4 with DN, after controlling for key covariates. Conclusion: The results of this case-control study provide evidence that the epsilon 2 and epsilon 3 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.