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Influence of Apolipoprotein E Genotype on Progression of Diabetic Nephropathy

Aims: Diabetic nephropathy progresses at a variable rate part of which may be explained by genetic polymorphisms. ApoE polymorphisms are associated with progression of atherosclerosis and because of the similarities between atherosclerosis and glomerulosclerosis, we chose to examine apoE and its role in progression of diabetic nephropathy. Methods: The apoE genotypes of 90 patients with type 2 diabetes and nephropathy who were recruited into a 2-year prospective randomised controlled study comparing intensive medical management with routine clinical care were analysed. The primary endpoint was the rate of progression of renal disease in the second year. Results: The apoE genotype frequencies were 49 with E3/3, 20 with E2/3, 17 with E3/4 and 4 with of E2/4. There were no significant differences in age, degree of renal failure, BP, albuminuria or glycaemic control between any genotype. The rate of progression of renal failure of patients with the E3/4 genotype was 0.80 ml/min/month compared to 0.30 ml/min/month for E2/3 and 0.18 ml/min/month for those with E3/3. Patients with E3/4 genotype had significantly faster rates of progression in the second year when compared with the other 3 genotypes (0.80 vs. 0.25 ml/min/month, p = 0.012). There was no difference in mortality according to apoE genotype. Conclusion: Patients who possess the apoE3/4 genotype had significantly faster rates of progression of renal failure.