Apolipoprotein E polymorphism and renal disease

Background. Lipid abnormalities are frequently found in end-stage renal dis ease (ESRD), and abnormal lipid metabolism may contribute to the progressio n of renal disease. Previous investigators have reported that apolipoprotei n E (apoE) has an important role in lipoprotein metabolism and that the pro cess of lipoprotein catabolism varies according to the apoE phenotype. In a ddition, the relative frequency of the apoE alleles is different among the races. In this study, we investigated the allele frequency of apoE phenotyp es and evaluated the impact of apoE polymorphism on lipid profile in Japane se patients with renal disease. Methods. ApoE phenotypes were determined using isoelectric focusing and Wes tern blotting in 592 Japanese patients with renal disease [86 out of 107 pa tients with glomerulonephritis had proteinuria of not less than 0.25 g per 24 hr and 485 with ESRD; 448 were on hemodialysis (HD), and 37 were on cont inuous ambulatory peritoneal dialysis (CAPP)I. The allele frequency and apo E phenotype distribution were estimated by the gene-counting method. Serum lipid parameters related to lipid metabolism were measured after at least a 12-hour fast. Results. The allele frequency of the three major apoE phenotypes (apoE2, ap oE3, and apoE4) in 107 glomerulonephritis patients (epsilon 2; 0.037, epsil on 3; 0.860, epsilon 4; 0.103) was almost identical to that in the normal c ontrol population (epsilon 2; 0.036, epsilon 3; 0.848, epsilon 4; 0.115). H owever, 86 glomerulonephritis patients with proteinuria had higher allele f requency of apoE2 (epsilon 2; 0.052, P < 0.01) and apoE4 (epsilon 4; 0.140, P < 0.001) and lower allele frequency of apoE3 (epsilon 3; 0.808, P < 0.00 1) than the controls. Furthermore, ESRD patients had higher allele frequenc y of apoE2 (epsilon 2; 0.058, P < 0.01) and lower allele frequency of apoE4 (epsilon 4; 0.091, P < 0.05) than the controls. Higher prevalence of nephr otic syndrome was found in proteinuric glomerulonephritis patients with apo E2. The impact of apoE polymorphism on serum lipid profile in patients with glomerulonephritis, HD, and CAPD was different from that generally expecte d. Conclusions. The higher frequency of apoE2 in ESRD patients suggests that a poE2 is a possible genetic predisposition to ESRD in a Japanese population. The impact of apoE2 and apoE4 on lipid profile in patients with renal dise ase was unique and different from that in the normal population.