APOE polymorphisms and the development of diabetic nephropathy in type 1 diabetes - Results of case-control and family-based studies

The goal. of this study was to examine the association between known polymo rphisms in the apolipoprotein E gene (APOE) and diabetic nephropathy (DN) i n type 1 diabetes. We used both a case-control comparison and a family-base d study design known as the transmission/disequilibrium test (TDT). For the case-control comparison, me collected DNA from 223 subjects with clinicall y diagnosed DN and 196 control subjects with normoalbuminuria and long-dura tion type I diabetes (greater than or equal to 15 years). For the family-ba sed study, we obtained DNA hom both parents of 154 DN subjects and 81 contr ol subjects. The frequency of the epsilon2 allele of exon 4 of APOE was sig nificantly higher in DN subjects than in control subjects. The risk of DN w as 3.1 times higher (95% CI 1.6-5.9) in carriers of this allele than in non carriers. In the family study, heterozygous parents for the epsilon2 allele preferentially transmitted epsilon2 to DN offspring (64 vs. 36%,P < 0.03). Four additional polymorphisms (i.e., -491 A/T-219 G/T, IE1 G/C, and APOCI insertion/deletion [I/D]) that flank the APOE locus mere not associated wit h DN in either the case-control comparison or in the family-based study. In conclusion, the results of the case-control as web as the family-based stu dy provide evidence that the <epsilon>2 allele of APOE increases the risk o f DN in type 1 diabetes. The molecular mechanisms underlying this risk are unclear at present.