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NDT Advance Access published online on February 14, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn734
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Apolipoprotein E polymorphism and expression in type 2 diabetic patients with nephropathy: clinicopathological correlation

Jing Guan1, Hai-Lu Zhao1, Larry Baum1, Yi Sui1, Lan He1, Harriet Wong1, Fernand M. M. Lai2, Peter C. Y. Tong1,3 and Juliana C. N. Chan1,3,4

1 Department of Medicine and Therapeutics, The Prince of Wales hospital, The Chinese University of Hong Kong, Hong Kong SAR, China 2 Department of Anatomical and Cellular Pathology, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China 3 Hong Kong Institute of Diabetes & Obesity 4 Li Ka Shing Institute of Health Sciences, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China

Correspondence and offprint requests to: Juliana CN Chan, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. Tel: +852-2632-3138; Fax: +852-2632-3108; E-mail: jchan{at}cuhk.edu.hk



  Abstract

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 autopsies of patients with type 2 diabetes.

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, {varepsilon}2 carriers (P = 0.04; odds ratio = 5.42; 95% CI: 1.10–26.8) and {varepsilon}3/{varepsilon}4 (P = 0.04; odds ratio = 22.5; 95% CI: 1.11–454.90) genotype carriers were more likely to have glomerular hypertrophy than were {varepsilon}3/{varepsilon}3 carriers. The {varepsilon}2 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.

Keywords: apolipoprotein E; diabetic nephropathy; glomerulopathy

Received for publication: 9. 9.08
Accepted in revised form: 8.12.08


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