Background/Aim: Cytokines play an important role in the pathogenesis of kidney diseases. The aim of the study was to investigate the impact of interleukin (IL)-1 cluster genes on diabetic nephropathy in Korean patients with type 2 diabetes mellitus (DM). Methods: We investigated –511 C/T polymorphism of IL-1β and tandem repeat polymorphism in intron 2 of IL-1 receptor antagonist in type 2 DM patients with end-stage kidney failure as compared with patients without nephropathy. Results: The IL1B2 allele was found more frequently in patients with kidney failure than in controls (57.4 vs. 46.1%, p < 0.05). An excessive homozygous carriage of IL1B2 was found in patients with kidney failure when compared with controls (30.5 vs. 18.3%, p < 0.05). The allelic frequency of IL1RN*2 was also higher in cases than in controls without nephropathy (8.4 vs. 2.8 %, p < 0.05). The carriage rate of IL1RN*2 was significantly associated with an increased risk of kidney failure (15.8 vs. 5.6%; OR 3.19, 95% CI 1.24–8.17). The risk of kidney failure was highest in those carrying both IL1RN*2 and IL1B2 (OR 3.90, 95% CI 1.34–11.40). Conclusion: IL1B2 and IL1RN*2 genotypes of the IL-1 cluster genes are associated with diabetic nephropathy in Korean patients with type 2 DM.

Cowie CC, Port FK, Wolfe RA, Savage PJ, Moll PP, Hawthorne VM: Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med 1989;321:1074–1079.
Ritz E, Orth SR: Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med 1999;341:1127–1133.
Molitch ME: Management of early diabetic nephropathy. Am J Med 1997;102:392–398.
Hovind P, Rossing P, Tarnow L, Smidt UM, Parving HH: Progression of diabetic nephropathy. Kidney Int 2001;59:702–709.
Watts GF, Taub N, Gant V, Wilson I, Shaw KM: The immunogenetics of early nephropathy in insulin-dependent diabetes mellitus: Association between the HLA-A2 antigen and albuminuria. Q J Med 1992;83:461–471.
Lovati E, Richard A, Frey BM, Frey FJ, Ferrari P: Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. Kidney Int 2001;60:46–54.
Freedman BI, Yu H, Spray BJ, Rich SS, Rothschild CB, Bowden DW: Genetic linkage analysis of growth factor loci and end-stage renal disease in African Americans. Kidney Int 1997;51:819–825.
Hurme M, Lahdenpohja N, Santtila S: Gene polymorphisms of interleukins 1 and 10 in infectious and autoimmune diseases. Ann Med 1998;30:469–473.
Mansfield JC, Holden H, Tarlow JK, Di Giovine FS, McDowell TL, Wilson AG, Holdsworth CD, Duff GW: Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology 1994;106:637–642.
Mira JP, Cariou A, Grall F, et al: Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: A multicenter study. JAMA 1999;282:561–568.
Hasegawa G, Nakano K, Sawada M, Uno K, Shibayama Y, Ienaga K, Kondo M: Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy. Kidney Int 1991;40:1007–1012.
Shu KH, Lee SH, Cheng CH, Wu MJ, Lian JD: Impact of interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphism on IgA nephropathy. Kidney Int 2000;58:783–789.
Syrjänen J, Hurme M, Lehtimäki T, Mustonen J, Pasternack A: Polymorphism of the cytokine genes and IgA nephropathy. Kidney Int 2002;61:1079–1085.
Melcion C, Lachman L, Killen PD, Morel-Maroger L, Striker GE: Mesangial cells, effect of monocyte products on proliferation and matrix synthesis. Transplant Proc 1982;14:559–564.
Blakemore AI, Cox A, Gonzalez AM, Maskil JK, Hughes ME, Wilson RM, Ward JD, Duff GW: Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus. Hum Genet 1996;97:369–374.
Loughrey BV, Maxwell AP, Fogarty DG, Middleton D, Harron JC, Patterson CC, Darke C, Savage DA: An interleukin 1B allele, which correlates with a high secretor phenotype, is associated with diabetic nephropathy. Cytokine 1998;10:984–988.
Di Giovine FS, Takhsh E, Blakemore AI, Duff GW: Single base polymorphism at –511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1992;1:450.
Dinarello CA, Wolff SM: The role of interleukin-1 in disease. N Engl J Med 1993;328:106–113.
Tarnow L, Pociot F, Hansen PM, Rossing P, Nielsen FS, Hansen BV, Parving HH: Polymorphisms in the interleukin-1 gene cluster do not contribute to the genetic susceptibility of diabetic nephropathy in Caucasian patients with IDDM. Diabetes 1997;46:1075–1076.
Bensen JT, Langefeld CD, Hawkins GA, et al: Nucleotide variation, haplotype structure, and association with end-stage renal disease of the human interleukin-1 gene cluster. Genomics 2003;82:194–217.
Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T: Diabetic nephropathy in type 1 (insulin-dependent) diabetes: An epidemiological study. Diabetologia 1983;25:496–501.
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.