Apolipoprotein E gene polymorphism, hypercholesterolemia and glomerular filtration rate in type 2 diabetic subjects: a 9-year follow-up study.
OBJECTIVE
To study the association between apolipoprotein E (apoE) genotype and the rate of decline in glomerular filtration rate (GFR) in type 2 diabetic patients in a 9-year prospective study.


METHODS
GFR was determined in 84 type 2 diabetic patients by plasma clearance of (51)Cr-EDTA at baseline and after 9 years of follow-up. ApoE genotypes were determined by polymerase chain reaction and restriction enzyme HHAI digestion and designated as epsilon4 allele group (apoE4/2, 4/3 and 4/4 genotypes; n = 20) and non-epsilon4 allele group (apoE3/3 and E3/2 genotypes; n = 64). We focused our analysis on those patients who were more likely to progress to diabetic renal disease, i.e. whose GFR fell more than expected in the normal course of ageing [1 ml x min(-1) x (1.73 m(2))(-1) per year].


RESULTS
In the whole population, the decline in the GFR did not differ statistically significantly between the apoE genotype groups [p = 0.65 with analysis of variance for repeated variables (RANOVA) for interaction between apoE genotype group and time point]. However, among patients whose GFR changed more than 9 ml x min(-1) x (1.73 m(2))(-1), GFR showed a statistically significantly greater decline in the epsilon4 allele group (n = 11) than in the non-epsilon4 allele group (n = 43) [from 116 +/- 36 to 80 +/- 29 ml x min(-1) x (1.73 m(2))(-1) vs. from 119 +/- 20 to 96 +/- 18 ml x min(-1) x (1.73 m(2))(-1); p = 0.005 with RANOVA].


CONCLUSIONS
ApoE allele epsilon4 may speed up the rate of decline of the GFR in patients with progressive diabetic renal disease.
Lehtinen
Saara
S
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere, Finland. saaral@sci.fi
Rantalaiho
Vappu
V
Wirta
Ole
O
Pasternack
Amos
A
Laippala
Pekka
P
Koivula
Timo
T
Lehtimäki
Terho
T
D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013997:Time Factors
D001057:Apolipoproteins E