Background/Aims: The Hp1/Hp2 DNA polymorphism has previously been implicated in susceptibility to diabetic nephropathy in some but not all studies. In an attempt to clarify these conflicting findings, we conducted a case-control association study in a Caucasian population. Methods: We recruited 224 and 285 type 1 diabetic patients with (cases) and without (controls) nephropathy, respectively, from 2 centres based in Northern Ireland and the Republic of Ireland. Hp1/Hp2 genotyping was performed using a combination of long-range and multiplex PCR. Allele and genotype frequencies in cases and controls were compared using the χ2 test. Results: There was a statistically significant increase in the frequency of the Hp2 allele in cases compared to controls (65.6 vs. 58.6%, OR = 1.35, 95% CI: 1.04–1.76, p = 0.03). The distributions of genotypes were in Hardy-Weinberg equilibrium for both cases and controls, and the overall frequency of the Hp1 allele was 38.3%, which is similar to that found in other Western European populations. Conclusions: The results suggest that the Hp2 allele may confer susceptibility to nephropathy in patients with type 1 diabetes.

Keywords:
Diabetic nephropathy, Genetic susceptibility, Gene polymorphism, Oxidative stress
1.
U.S. Renal Data System, USRDS 2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2005.
2.
Seaquist ER, Goetz FC, Rich S, Barbosa J: Familial clustering of diabetic kidney disease: evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 1989;320:1161–1165.
3.
Quinn M, Angelico MC, Warram JH, Krolewski AS: Familial factors determine the development of nephropathy in patients with IDDM. Diabetologia 1996;39:940–945.
4.
Lee HB, Yu MR, Yang Y, Jaing Z, Ha H: Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. J Am Soc Nephrol 2003;14:S241–S245.
5.
Langlois MR, Delanghe JR: Biological and clinical significance of haptoglobin polymorphisms in humans. Clin Chem 1996;42:1589–1600.
6.
Levy AP, Roguin A, Hochberg I, et al: Haptoglobin phenotype and vascular complications in patients with diabetes. N Engl J Med 2000;343:969–970.
7.
Nakhoul FM, Zoabi R, Kanter Y, et al: Haptoglobin phenotype and diabetic nephropathy. Diabetologia 2001;44:602–604.
8.
Moczulski DK, Rogus JJ, Krolewski AS: Haptoglobin phenotype and diabetes. Diabetologia 2001;44:2237–2239.
9.
Koda Y, Soejima M, Yamagishi S, et al: Haptoglobin genotype and diabetic microangiopathies in Japanese diabetic patients. Diabetologia 2002;45:1039–1040.
10.
Conway BR, Maxwell AP, Savage DA, et al: Association between variation in the actin-binding gene caldesmon and diabetic nephropathy in type 1 diabetes. Diabetes 2004;53:1162–1165.
© 2007 S. Karger AG, Basel
2007
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.