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Rheumatology Advance Access originally published online on September 26, 2006
Rheumatology 2007 46(3):426-430; doi:10.1093/rheumatology/kel331
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility

R. López-Arbesu, F. J. Ballina-García1, M. Alperi-López1, A. López-Soto, S. Rodríguez-Rodero2, J. Martínez-Borra2, A. López-Vázquez2, J. L. Fernández-Morera2, J. L. Riestra-Noriega1, R. Queiro-Silva1, A. Quiñones-Lombraña, C. López-Larrea and S. González

Department of Functional Biology, University of Oviedo, 1Department of Rheumatology and 2Histocompatibility and Transplantation Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

Correspondence to: Segundo González, MD, PhD, Department of Functional Biology, Instituto Oncológico del principado de Asturias, Universidad de Oviedo, Facultad de Medicina, Julián Clavería sn, 33006, Oviedo, Spain. E-mail: segundog{at}uniovi.es


  Abstract

Objectives. Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of {kappa}B-like (I{kappa}BL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA.

Methods. A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism –62 of the I{kappa}BL gene.

Results. A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, Pc = 0.01, OR = 2.1, 95% CI = 1.3–3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, Pc = 0.04, OR = 3.2, 95% CI = 1.3–8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, Pc = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, Pc = 0.01, OR = 2.2, 95% CI = 1.3–3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 ({lambda}s = 0.33) and HLA-DRB1*0405 ({lambda}s = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between I{kappa}BL and MICA with RA was found.

Conclusions. MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.

KEY WORDS: Rheumatoid arthritis, MHC, HLA-DR, MICB, MICA, I{kappa}BL

Submitted 21 July 2006; revised version accepted 15 August 2006.
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