Genetic susceptibility contributes to the development of diabetic nephropathy. In considering potentially important genetic factors, this study examined the association between genetic polymorphisms in apolipoprotein (apo) E and diabetic nephropathy in 146 patients with insulin-dependent diabetes mellitus (IDDM) of 15 to 21 years' duration. Using a case-control study design, patients with proteinuria (N = 41) (albumin excretion rate (AER) > or = 250 micrograms/min) and patients with microalbuminuria (N = 31) (AER 20 to 250 micrograms/min) were compared with patients who had normoalbuminuria (N = 74) (AER < 20 micrograms/min). Genetic polymorphisms at the apo E locus were identified by the method of denaturing gradient-gel electrophoresis. There was no significant difference in allele frequencies in the proteinuric, microalbuminuric, or normoalbuminuric groups (e2 7.3%, 9.7%, 9.5%; e3 78.1%, 72.6%, 68.2%; e4 14.6%, 17.7%, 22.3%; respectively). The distribution of the apo E genotypes among the three groups of patients was also similar. These results suggest that apo E genotypes are not associated with the development of early or advanced diabetic nephropathy in patients with IDDM.