APOLIPOPROTEIN E4 REDUCES RISK OF DIABETIC NEPHROPATHY IN PATIENTS WITH NIDDM

Hypercholesterolemia is a major determinant of the decline of renal fu nction in patients with diabetes, Apolipoprotein E polymorphism may in fluence the metabolism of lipoprotein in diabetic patients. The purpos e of this study was to investigate the association between genetic pol ymorphisms in apolipoprotein E and the progression of diabetic nephrop athy in patients with non-insulin-dependent diabetes mellitus over a 1 0-year period (13 to 37 years; median, 20 years), Subjects with a stab le renal function without overt proteinuria had a higher cholesterol l evel, lower incidences of hypertension and proliferative diabetic reti nopathy, and a higher frequency of the E4 allele than subjects with a decline in renal function (end-stage renal failure requiring dialysis treatment), In the diabetic patients, the apolipoprotein E4 carriers h ad a higher cholesterol level than did the noncarriers. The survival r ate from renal disease in the apolipoprotein E4 carriers was higher th an in the noncarriers among the diabetic patients, Apolipoprotein E po lymorphism and hypertension were identified as independent risk factor s for the progression to renal failure, Results indicate that apolipop rotein E polymorphism is associated with the progression of diabetic n ephropathy, Presence of the apolipoprotein E4 allele is a protective f actor, and other alleles are risk factors. (C) 1998 by the National Ki dney Foundation, Inc.