title: Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA)--positive rheumatoid arthritis in three Asian ethnic groups.
abstract: BACKGROUND
  To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.
  
  
  METHODS
  1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.
  
  
  RESULTS
  The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.
  
  
  CONCLUSIONS
  The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Too
authors.initials: T
authors.lastname: Chun-Lai
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Jasbir Singh
authors.initials: JS
authors.lastname: Dhaliwal
authors.forename: Emeli
authors.initials: E
authors.lastname: Lundström
authors.forename: Abqariyah
authors.initials: A
authors.lastname: Yahya
authors.forename: Nor Asiah
authors.initials: NA
authors.lastname: Muhamad
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Per Tobias
authors.initials: PT
authors.lastname: Larsson
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Murad
mesh_terms: D000483:Alleles; D000906:Antibodies / Q000737:chemistry / Q000235:genetics*; D001208:Asia / Q000208:ethnology; D002956:Citrulline / Q000276:immunology*; D000939:Epitopes / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D012217:Rheumatoid Factor / Q000276:immunology; D012307:Risk Factors
chemical_list: D000906:Antibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553514:HLA-DRB1*12:02 antigen; D002956:Citrulline; D012217:Rheumatoid Factor