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Influence of HLA-DRB1 Genes and the Shared Epitope on Genetic Susceptibility to Rheumatoid Arthritis in Taiwanese
SHIH-CHIA LIU, TZU-YANG CHANG, YANN-JINN LEE, CHEN-CHUNG CHU, MARIE LIN, ZONG-XIAN CHEN, HSIN-FU LIU, CHING-WEN DANG, SHIH-CHUAN CHANG, CHYOU-SHEN LEE, TIEN-LING CHEN, and CHUN-HSIUNG HUANG ABSTRACT. Objective. To investigate the association of predisposing and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in a Taiwanese population. Methods. A total of 273 patients with RA and 480 healthy controls, all of Taiwanese origin, were genotyped for HLA-DRB1 alleles by polymerase chain reaction and sequence-based typing assays. The associations between RA and HLA-DRB1 alleles and genotypes were investigated by chi-squared test. Results. The DRB1*0405 and *1001 phenotypes showed the most significant associations with RA (OR 4.04, 95% CI 2.84–5.77, pc = 3.2 ´ 10-14; OR 5.25, 95% CI 2.10–13.06, pc = 3.0 ´ 10-3, respectively). Individuals carrying single or double doses of the shared epitope (SE/non-SE or SE/SE) had higher risks of RA. The compound heterozygote of DRB1*0405/*1001 showed the largest increase in RA risk (OR 15.8, 95% CI 2.48–100.7, pc = 0.004). Single or double doses of SE alleles were significantly associated with a higher bone erosion rate. Rheumatoid factor positivity and bone erosion were more frequent in patients with at least one copy of DRB1*0405. Conclusion. Our results show that SE-encoding HLA-DRB1*0405 and *1001 are associated with RA in a Taiwanese population; this is the first time DRB1*1001 has been described in persons of Asian ethnicity. Heterozygotes of DRB1*0405 and *1001 predicted the strongest susceptibility to RA, suggesting that this genotype enhances susceptibility to RA in Taiwanese. (First Release Feb 15 2007; J Rheumatol 2007;34:674–80) Key Indexing Terms:
HLA-DRB1 From the Department of Orthopedic Surgery, Department of Medical Research, Department of Pediatrics, and Department of Rheumatology, Mackay Memorial Hospital, Taipei; Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei; and College of Medicine, Yang-Ming University, Taipei, Taiwan. Supported by grants MMH 9267 and E-95007 from Mackay Memorial Hospital, Taiwan. S.C. Liu, MD, Orthopedist, Department of Orthopedic Surgery; T.Y. Chang, PhD, Associate Researcher; C.C. Chu, PhD, Associate Researcher; M. Lin, MD, Senior Scientist; Z.X. Chen, MS, Assistant Researcher; H.F. Liu, PhD, Associate Researcher; C.W. Dang, MS, Assistant Researcher; S.C. Chang, BS, Assistant Researcher, Department of Medical Research; Y.J. Lee, MD, MS, Pediatrician, Departments of Medical Research and Pediatrics; C.S. Lee, MD, Rheumatologist; T.L. Chen, MD, Rheumatologist, Department of Rheumatology; C.H. Huang, MD, Orthopedist, Department of Orthopedic Surgery, President, Mackay Memorial Hospital, College of Medicine, Yang-Ming University. Address reprint requests to Dr. C.H. Huang, Department of Orthopedic Surgery, Mackay Memorial Hospital, Chung-Sun North Road, Sec. 2, Taipei 104, Taiwan. E-mail: chhuang@ms2.mmh.org.tw Accepted for publication December 12, 2006.
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