Background: The phospholipase A2 receptor (PLA2R) is a major antigen found in patients with idiopathic membranous nephropathy (MN). The relationship of genetic polymorphisms of PLA2R with the susceptibility and clinical outcomes of this disease is unknown. Methods: We studied 199 patients with idiopathic MN followed up for 3.7 ± 3.2 years. We enrolled 33 patients with secondary MN and 356 subjects with normal blood pressure and no proteinuria. PLA2R single nucleotide polymorphisms (SNPs) were genotyped. Results: The allele frequencies of C in rs35771982 and G in rs3828323 were 73.6 and 73.9%, respectively. Subjects with the CC genotype in rs35771982 had a higher susceptibility to idiopathic MN compared to subjects with other genotypes (odds ratio 2.6; 95% confidence interval 1.8–4.0). Patients with secondary MN were not different from controls with regard to PLA2R genotype. No impact of genetic polymorphisms on renal survival was detected. Conclusion: The findings of this study suggest that PLA2R SNPs might be associated with the risk of developing MN.

Keywords:
Genetic polymorphism, Glomerulonephritis, Membranous nephropathy, Phospholipase A2 receptor
1.
Bantis C, Heering PJ, Aker S, Siekierka M, Kuhr N, Grabensee B, Ivens K: Tumor necrosis factor-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis. Am J Nephrol 2006;26:12–15.
2.
Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009;361:11–21.
3.
Ancian P, Lambeau G, Mattei MG, Lazdunski M: The human 180-kDa receptor for secretory phospholipases A2. Molecular cloning, identification of a secreted soluble form, expression, and chromosomal localization. J Biol Chem 1995;270:8963–8970.
4.
Ishizaki J, Hanasaki K, Higashino K, Kishino J, Kikuchi N, Ohara O, Arita H: Molecular cloning of pancreatic group I phospholipase A2 receptor. J Biol Chem 1994;269:5897–5904.
5.
Chin HJ, Cho HJ, Lee TW, Na KY, Yoon HJ, Chae DW, Kim S, Jeon US, Do JY, Park JW, Yoon KW, Shin YT, Lee KW, Na KR, Cha DR, Kang YS: The heme oxygenase-1 genotype is a risk factor to renal impairment of IgA nephropathy at diagnosis, which is a strong predictor of mortality. J Korean Med Sci 2009;24(suppl):S30–S37.
6.
Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G: Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;67:2089–2100.
7.
Taylor ME, Conary JT, Lennartz MR, Stahl PD, Drickamer K: Primary structure of the mannose receptor contains multiple motifs resembling carbohydrate-recognition domains. J Biol Chem 1990;265:12156–12162.
8.
Drickamer K: Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem 1988;263:9557–9560.
9.
Mayer RJ, Marshall LA: New insights on mammalian phospholipase A2(s); comparison of arachidonoyl-selective and -nonselective enzymes. FASEB J 1993;7:339–348.
10.
Hourcade D, Miesner DR, Atkinson JP, Holers VM: Identification of an alternative polyadenylation site in the human C3b/C4b receptor (complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1. J Exp Med 1988;168:1255–1270.
11.
Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini S, Remuzzi G: Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 1993;329:85–89.
12.
Shiiki H, Saito T, Nishitani Y, Mitarai T, Yorioka N, Yoshimura A, Yokoyama H, Nishi S, Tomino Y, Kurokawa K, Sakai H: Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int 2004;65:1400–1407.
13.
Troyanov S, Roasio L, Pandes M, Herzenberg AM, Cattran DC: Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int 2006;69:1641–1648.
14.
Braden GL, Mulhern JG, O’Shea MH, Nash SV, Ucci AA Jr, Germain MJ: Changing incidence of glomerular diseases in adults. Am J Kidney Dis 2000;35:878–883.
15.
Korbet SM, Genchi RM, Borok RZ, Schwartz MM: The racial prevalence of glomerular lesions in nephrotic adults. Am J Kidney Dis 1996;27:647–651.
16.
Rivera F, Lopez-Gomez JM, Perez-Garcia R: Clinicopathologic correlations of renal pathology in Spain. Kidney Int 2004;66:898–904.
17.
Ohara O, Ishizaki J, Arita H: Structure and function of phospholipase A2 receptor. Prog Lipid Res 1995;34:117–138.
© 2010 S. Karger AG, Basel
2010
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.