Association of HLA class II genes with systemic sclerosis in Koreans

Objective, To investigate HLA class II associations with systemic sclerosis (SSc) in Koreans according to anti-topoisomerase I(anti-topo I), anti-cent romere antibody (ACA), and anti-U1 ribonucleoprotein (RNP) status, Methods. HLA class II alleles (DRB1, DRB5, DQB1) were determined by DNA typ ing in 200 healthy control subjects and 74 patients with SSc: 35 anti-topo I positive, 3 ACA positive, and 19 anti-Ui 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 co mpared with both controls (23% vs 5%; P-corr = 0.003) and anti-topo I negat ive patients (23% vs 3%; p = 0.009); our study confirms observations in Jap anese. HLA-DR (FLEDR71)-F-67, especially V-38-(FLEDR71)-F-67 sequence (carr ied on DRB5*0102 in linkage disequilibrium with DRB1*1502, DRB1*0802, DR81* 1101), showed the strongest association with anti-topo I response (46% vs 1 6% in controls; p(corr) = 0.001), and L-38-(FLEDR71)-F-67 group alleles wer e not associated with anti-topo I response, Anti-topo I response was not si gnificantly associated with HLA-DQB 1 alleles in Koreans. There were only 3 ACA positive patients, and all patients had DRB1*1501 and DQB1*0602 as het erozygotes. Anti-U1 RNP occurred at a high frequency (63%) among patients w ith 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 si gnificantly associated with DRB1*0803 (47% vs 15% in controls; p(corr) < 0. 05) and DRB1*1501 (50% vs 17% in controls; p(corr) < 0.01), respectively. T hese HLA associations have not been reported in other ethnic groups and pos sible associations with certain autoantibody subsets remain to be confirmed . Conclusion, HLA-DR gene has a primary association with anti-topo I response , and HLA-DR V-38-(FLEDR71)-F-67 group alleles including DRB5*0102 tin link age disequilibrium with DRB1*1502) show the strongest association with anti -topo I response in Korean patients with SSc.