title: Association of HLA class II genes with systemic sclerosis in Koreans.
abstract: OBJECTIVE
  To investigate HLA class II associations with systemic sclerosis (SSc) in Koreans according to anti-topoisomerase I (anti-topo I), anti-centromere antibody (ACA), and anti-U1 ribonucleoprotein (RNP) status.
  
  
  METHODS
  HLA class II alleles (DRB1, DRB5, DQB1) were determined by DNA typing in 200 healthy control subjects and 74 patients with SSc: 35 anti-topo I positive, 3 ACA positive, and 19 anti-U1 RNP positive; among them were 34 diffuse and 40 limited subtypes, and 16 overlap syndrome.
  
  
  RESULTS
  Anti-topo I positive SSc was strongly associated with DRB1*1502 compared with both controls (23% vs 5%; Pcorr = 0.003) and anti-topo I negative patients (23% vs 3%; p = 0.009); our study confirms observations in Japanese. HLA-DR 67FLEDR71, especially 38V-67FLEDR71 sequence (carried on DRB5*0102 in linkage disequilibrium with DRB1*1502, DRB1*0802, DRBI*1101), showed the strongest association with anti-topo I response (46% vs 16% in controls; Pcorr = 0.001), and 38L-67FLEDR71 group alleles were not associated with anti-topo I response. Anti-topo I response was not significantly associated with HLA-DQB1 alleles in Koreans. There were only 3 ACA positive patients, and all patients had DRB1*1501 and DQB1*0602 as heterozygotes. Anti-U1 RNP occurred at a high frequency (63%) among patients with overlap syndrome, and was not associated with HLA-DR or DQ genes. Among anti-topo I negative patients, diffuse and limited subtypes of SSc were significantly associated with DRB1*0803 (47% vs 15% in controls; Pcorr < 0.05) and DRB1*1501 (50% vs 17% in controls; Pcorr < 0.01), respectively. These HLA associations have not been reported in other ethnic groups and possible associations with certain autoantibody subsets remain to be confirmed.
  
  
  CONCLUSIONS
  HLA-DR gene has a primary association with anti-topo I response, and HLA-DR 38V-67FLEDR71 group alleles including DRB5*0102 (in linkage disequilibrium with DRB1*1502) show the strongest association with anti-topo I response in Korean patients with SSc.
authors.affiliation: Department of Clinical Pathology, Seoul National University College of Medicine, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kang
authors.forename: M H
authors.initials: MH
authors.lastname: Park
authors.forename: E Y
authors.initials: EY
authors.lastname: Song
authors.forename: S J
authors.initials: SJ
authors.lastname: Kang
authors.forename: E B
authors.initials: EB
authors.lastname: Lee
authors.forename: Y W
authors.initials: YW
authors.lastname: Song
authors.forename: F
authors.initials: F
authors.lastname: Takeuchi
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D002503:Centromere / Q000276:immunology; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D059847:HLA-DRB5 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059847:HLA-DRB5 Chains; D000949:Histocompatibility Antigens Class II; D017412:Ribonucleoprotein, U1 Small Nuclear; D004264:DNA Topoisomerases, Type I