DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese

Abstract

Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis with unknown pathogenesis. Accumulating evidences have shown the ethnic-specific association between certain human leukocyte antigen (HLA) alleles and IgAN susceptibility. This study was designed to explore the relationship between HLA-DQB1 alleles and disease susceptibility and clinical manifestations of patients with IgAN in southern Han Chinese. A PCR sequence-based typing technique was used to detect HLA-DQB1 alleles in 217 IgAN patients and 229 healthy subjects. Clinical data were collected from each patient at the time of renal biopsy. Twenty HLA-DQB1 alleles were detected in IgAN patients and healthy subjects. High frequency of HLA-DQB1*060101 and low frequency of HLA-DQB1*030101 were observed in IgAN patients compared with healthy controls. Further stratification analysis revealed that the frequency of DQB1*060101 was significantly higher in patients with urine protein≥1.0 g/24 h than in patients with urine protein<1.0 g/24 h. In combination with our previous DRB1 results, we also analyzed the association of DRB1-DQB1 haplotypes with IgAN. We found that the frequency of haplotype DRB1*090102-DQB1*060101 was significantly higher [odds ratio (OR) = 4.409, Pc = 0.016], whereas that of HLA-DRB1*070101-DQB1*020101 was significantly lower (OR= 0.194, Pc = 0.016) compared with healthy controls. Our study indicated that HLA-DQB1*060101 alleles may be a potential predictor of high-risk IgAN susceptibility in Chinese Han population.

Keywords

DQB1 / human leukocyte antigen (HLA) / IgA nephropathy / haplotype / association study

References

[1] Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol 2005; 16(7): 2088–2097

[2] Donadio JV, Grande JP. IgA nephropathy. N Engl J Med 2002; 347(10): 738–748

[3] Mestecky J, Raska M, Julian BA, Gharavi AG, Renfrow MB, Moldoveanu Z, Novak L, Matousovic K, Novak J. IgA nephropathy: molecular mechanisms of the disease. Annu Rev Pathol 2013; 8(8): 217–240

[4] Szeto CC, Lai FM, To KF, Wong TY, Chow KM, Choi PC, Lui SF, Li PK. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med 2001; 110(6): 434–437

[5] Rantala I, Mustonen J, Hurme M, Syrjänen J, Helin H. Pathogenetic aspects of IgA nephropathy. Nephron 2001; 88(3): 193–198

[6] Hsu SI, Ramirez SB, Winn MP, Bonventre JV, Owen WF. Evidence for genetic factors in the development and progression of IgA nephropathy. Kidney Int 2000; 57(5): 1818–1835

[7] Maxwell PH, Wang Y. Genetic studies of IgA nephropathy. Nephron, Exp Nephrol 2006; 102(3-4): e76–e80

[8] Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, Khodiyar VK, Lush MJ, Povey S, Talbot CC Jr, Wright MW, Wain HM, Trowsdale J, Ziegler A, Beck S. Gene map of the extended human MHC. Nat Rev Genet 2004; 5(12): 889–899

[9] Floege J, Feehally J. IgA nephropathy: recent developments. J Am Soc Nephrol 2000; 11(12): 2395–2403

[10] Cao HX, Li M, Nie J, Wang W, Zhou SF, Yu XQ. Human leukocyte antigen DRB1 alleles predict risk and disease progression of immunoglobulin A nephropathy in Han Chinese. Am J Nephrol 2008; 28(4): 684–691

[11] Feehally J, Farrall M, Boland A, Gale DP, Gut I, Heath S, Kumar A, Peden JF, Maxwell PH, Morris DL, Padmanabhan S, Vyse TJ, Zawadzka A, Rees AJ, Lathrop M, Ratcliffe PJ. HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol 2010; 21(10): 1791–1797 doi:10.1681/ASN.2010010076 PMID:20595679

[12] Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 2011; 43(4): 321–327

[13] Yu XQ, Li M, Zhang H, Low HQ, Wei X, Wang JQ, Sun LD, Sim KS, Li Y, Foo JN, Wang W, Li ZJ, Yin XY, Tang XQ, Fan L, Chen J, Li RS, Wan JX, Liu ZS, Lou TQ, Zhu L, Huang XJ, Zhang XJ, Liu ZH, Liu JJ. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat Genet 2012; 44(2): 178–182

[14] Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M, Fasel D, Lata S, Prakash S, Shapiro S, Fischman C, Snyder HJ, Appel G, Izzi C, Viola BF, Dallera N, Del Vecchio L, Barlassina C, Salvi E, Bertinetto FE, Amoroso A, Savoldi S, Rocchietti M, Amore A, Peruzzi L, Coppo R, Salvadori M, Ravani P, Magistroni R, Ghiggeri GM, Caridi G, Bodria M, Lugani F, Allegri L, Delsante M, Maiorana M, Magnano A, Frasca G, Boer E, Boscutti G, Ponticelli C, Mignani R, Marcantoni C, Di Landro D, Santoro D, Pani A, Polci R, Feriozzi S, Chicca S, Galliani M, Gigante M, Gesualdo L, Zamboli P, Battaglia GG, Garozzo M, Maixnerová D, Tesar V, Eitner F, Rauen T, Floege J, Kovacs T, Nagy J, Mucha K, Pączek L, Zaniew M, Mizerska-Wasiak M, Roszkowska-Blaim M, Pawlaczyk K, Gale D, Barratt J, Thibaudin L, Berthoux F, Canaud G, Boland A, Metzger M, Panzer U, Suzuki H, Goto S, Narita I, Caliskan Y, Xie J, Hou P, Chen N, Zhang H, Wyatt RJ, Novak J, Julian BA, Feehally J, Stengel B, Cusi D, Lifton RP, Gharavi AG. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 2014; 46(11): 1187–1196

[15] Li M, Foo JN, Wang JQ, Low HQ, Tang XQ, Toh KY, Yin PR, Khor CC, Goh YF, Irwan ID, Xu RC, Andiappan AK, Bei JX, Rotzschke O, Chen MH, Cheng CY, Sun LD, Jiang GR, Wong TY, Lin HL, Aung T, Liao YH, Saw SM, Ye K, Ebstein RP, Chen QK, Shi W, Chew SH, Chen J, Zhang FR, Li SP, Xu G, Tai ES, Wang L, Chen N, Zhang XJ, Zeng YX, Zhang H, Liu ZH, Yu XQ, Liu JJ. Identification of new susceptibility loci for IgA nephropathy in Han Chinese. Nat Commun 2015; 6: 7270

[16] Churg J, Bernstein J, Glassock RJ. WHO Monograph. Renal Disease Classification and Atlas of Glomerular Disease.4th ed. New York: Ikagu Shoin Medical Publishers Inc, 1995

[17] Kotsch K, Wehling J, Blasczyk R. Sequencing of HLA class II genes based on the conserved diversity of the non-coding regions: sequencing based typing of HLA-DRB genes. Tissue Antigens 1999; 53(5): 486–497

[18] Lin JH, Liu ZH, Lv FJ, Fu YG, Fan XL, Li SY, Lu JM, Liu XY, Xu AL. Molecular analyses of HLA-DRB1, -DPB1, and-DQB1 in Jing ethnic minority of Southwest China. Hum Immunol 2003; 64(8): 830–834

[19] He YL, Zong LL, Peng DX, Liu ZH, Lin JH, Xu AL. Association of HLA-DPB1 gene with endometriosis in women of Guangdong Province in China. J First Mil Med Univ (Di Yi Jun Yi Da Xue Xue Bao) 2002; 22(5): 432–433（in Chinese）

[20] Schneider S, Roessli D, Excoffier L. Arlequin Version 2000: A Software for Population Genetics Data Analysis. Geneva, Switzerland: Genetics and Biometry Laboratory, University of Geneva, 2000

[21] Dean J, Dean A, Burton J. Public Domain Software For Epidemiology And Disease Surveillance. WHO AIDS Series, 1990

[22] Xiang Y, Gao Y, Wang T. Application and comparison of meta and pooled analyses in the study of cancer epidemiology. Chin J Oncol (Zhonghua Zhong Liu Za Zhi) 1999; 21(5): 354–358 (in Chinese) PMID:11776573

[23] Svejgaard A, Ryder LP. HLA and disease associations: detecting the strongest association. Tissue Antigens 1994; 43(1): 18–27

[24] Li PK, Burns AP, So AK, Pusey CD, Feehally J, Rees AJ. The DQw7 allele at the HLA-DQB locus is associated with susceptibility to IgA nephropathy in Caucasians. Kidney Int 1991; 39(5): 961–965

[25] Fennessy M, Hitman GA, Moore RH, Metcalfe K, Medcraft J, Sinico RA, Mustonen JT, D’Amico G. HLA-DQ gene polymorphism in primary IgA nephropathy in three European populations. Kidney Int 1996; 49(2): 477–480

[26] Park MH, Song EY, Ahn C, Oh KH, Yang J, Kang SJ, Lee HS. Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans. Tissue Antigens 2003; 62(6): 505–511

[27] Wu Y, Chen Y, Li L, Cao Y, Liu Z, Liu B, Du Z, Zhang Y, Chen S, Lin Z, Xu A. Polymorphic amino acids at codons 9 and 37 of HLA-DQB1 alleles may confer susceptibility to cervical cancer among Chinese women. Int J Cancer 2006; 118(12): 3006–3011

[28] Raguénès O, Mercier B, Clèdes J, Whebe B, Férec C. HLA class II typing and idiopathic IgA nephropathy (IgAN): DQB1*0301, a possible marker of unfavorable outcome. Tissue Antigens 1995; 45(4): 246–249

[29] Doxiadis II, De Lange P, De Vries E, Persijn GG, Claas FH. Protective and susceptible HLA polymorphisms in IgA nephropathy patients with end-stage renal failure. Tissue Antigens 2001; 57(4): 344–347

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg