Apolipoprotein E polymorphism and expression in type 2 diabetic patients with nephropathy: clinicopathological correlation.
BACKGROUND
Diabetic nephropathy represents a heterogeneous group of renal pathologies that may be associated with genetic susceptibility. There have been clinical reports on the risk association of diabetic nephropathy with an apolipoprotein E (ApoE) exon 4 polymorphism although its correlations with renal histopathological changes have not been explored.


METHODS
A total of 213 adult autopsies with type 2 diabetes and 111 non-diabetic control cases were analysed. Genomic DNA samples were obtained from spleen tissues. The ApoE genotype was determined by PCR-LDR analysis. Histopathological examination of kidney sections was performed in a subset of 51 diabetic and 111 control cases. ApoE protein expression in diabetic carriers with similar clinical status was examined by immunohistochemical staining.


RESULTS
In type 2 diabetes, epsilon2 carriers (P = 0.04; odds ratio = 5.42; 95% CI: 1.10-26.8) and epsilon3/epsilon4 (P = 0.04; odds ratio = 22.5; 95% CI: 1.11-454.90) genotype carriers were more likely to have glomerular hypertrophy than were epsilon3/epsilon3 carriers. The epsilon2 carriers showed an increase in glomerular ApoE protein expression. A correlation between ApoE genotype and nodular glomerulosclerosis was not found.


CONCLUSIONS
Our findings confirm the risk association of the ApoE polymorphism with diabetic nephropathy in clinical studies and is the first study demonstrating the correlations between ApoE genotypes, protein expression and structural changes in diabetic nephropathy.
Guan
Jing
J
Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
Zhao
Hai-Lu
HL
Baum
Larry
L
Sui
Yi
Y
He
Lan
L
Wong
Harriet
H
Lai
Fernand M M
FM
Tong
Peter C Y
PC
Chan
Juliana C N
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001344:Autopsy; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D001057:Apolipoproteins E; D017931:DNA Primers