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

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 e2, and higher Apo e4 allele frequencies was seen among T2DM patients than controls. Significantly higher frequency of e3/e4, and lower frequencies of e3/e3, e2/e3, and e4/e4 carriers was seen among T2DM cases. Apo e2-carrying individuals were more frequently found in controls than in patients, while significantly higher frequency of e4-carrying genotypes was seen in T2DM cases. Significantly higher e2, and lower e3 allele frequencies were noted for DN group compared to DWN group. Significantly higher frequency of e2-containing e2/e3 and e2/e4, and lower frequencies of e3/e3 carriers was seen among DN cases. Apo e3/e3 was associated with higher total cholesterol, LDL-cholesterol, and triglyceride levels in DN patients, and significantly higher triglyceride levels were seen in e2/e3-carrying DN patients. Logistic regression analysis confirmed the association of Apo e3-containing e3/e3, e2/e3, and e3/e4, and Apo e2-containing e2/e4 with DN, after controlling for key covariates. Conclusion The results of this case-control study provide evidence that the e2 and e3 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.