Apolipoprotein E polymorphism in 385 patients on renal replacement therapy in Sweden

To examine apolipoprotein (apo) E polymorphism and its possible link to kidney disease in all patients receiving renal replacement therapy in our region.

The apo E genotype, plasma (P) lipids, blood pressure and albumin excretion rate were determined retrospectively in 385 patients.

No differences in apo E genotype or the allelic frequencies of epsilon2, epsilon3 or epsilon4 were found between the patient group and a control group of 343 healthy individuals. The apo E3/E4 genotype, however, was found in only 1/24 patients with non-insulin-dependent diabetes mellitus (NIDDM), a significantly lower frequency than that seen in the rest of the patient group (p = 0.041). Similarly, the apo E4/E4 genotype was absent in patients with glomerulonephritis (GN) (p = 0.027). The relative frequency of the epsilon4 allele in patients with GN (0.116) was significantly lower than that in the rest of the patients (0.193; p < 0.05) and that in the control group (0.186; p = 0.027). Furthermore, 19/47 patients (40.4%) with autosomal dominant polycystic kidney disease (ADPKD) had the E3/E4 genotype, as compared to 77/338 (22.8%) in the rest of the patient group (p = 0.035; odds ratio 2.07; CI 1.09-3.92). An increase in the relative frequency of the epsilon4 allele was seen in the same diagnostic group: 0.29 vs 0.16 in the rest of the patient group (p = 0.0023). The mean P-cholesterol level in patients with the epsilon4 allele was 5.9 +/- 1.0 mmol/l, compared to 5.0 +/- 1.1 mmol/l in patients without the epsilon4 allele (p = 0.026).

In this study, variations in the frequencies of the apo epsilon4 allele and the apo E3/E4 and E4/E4 genotypes were found in patients with NIDDM, GN and ADPKD. This result may be a consequence of the effects of the apo epsilon4 and epsilon2 alleles on P-cholesterol and remnant lipoprotein levels. The decreased frequency of apo E3/E4 found in patients with NIDDM may be explained by the fact that the epsilon4 allele gives renoprotection against diabetic nephropathy by lowering plasma remnant lipoprotein levels. Conversely, there may be an association between the apo E3/E4 genotype and the epsilon4 allele in patients with ADPKD, due to the effect of the epsilon4 allele in elevating P-cholesterol levels. The most plausible explanation for the absence of the apo E4/E4 genotype and the lower prevalence of the epsilon4 allele in patients with GN, which is known to result in a higher P-cholesterol compared to the epsilon2 and epsilon3 alleles, ought to be an increase in cardiovascular morbidity, which is known to be associated with a higher P-cholesterol level.