Apolipoprotein E4 reduces risk of diabetic nephropathy in patients with NIDDM

Am J Kidney Dis. 1998 Apr;31(4):666-73. doi: 10.1053/ajkd.1998.v31.pm9531184.


Hypercholesterolemia is a major determinant of the decline of renal function in patients with diabetes. Apolipoprotein E polymorphism may influence the metabolism of lipoprotein in diabetic patients. The purpose of this study was to investigate the association between genetic polymorphisms in apolipoprotein E and the progression of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus over a 10-year period (13 to 37 years; median, 20 years). Subjects with a stable renal function without overt proteinuria had a higher cholesterol level, lower incidences of hypertension and proliferative diabetic retinopathy, 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 had a higher cholesterol level than did the noncarriers. The survival rate from renal disease in the apolipoprotein E4 carriers was higher than in the noncarriers among the diabetic patients. Apolipoprotein E polymorphism and hypertension were identified as independent risk factors for the progression to renal failure. Results indicate that apolipoprotein E polymorphism is associated with the progression of diabetic nephropathy. Presence of the apolipoprotein E4 allele is a protective factor, and other alleles are risk factors.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Apolipoprotein E4
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics*
  • DNA / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / genetics*
  • Disease Progression
  • Female
  • Genotype
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic / genetics
  • Renal Dialysis
  • Risk Factors
  • Time Factors


  • Apolipoprotein E4
  • Apolipoproteins E
  • DNA