Genetic risk and protective factors for idiopathic inflammatory myopathy in Koreans and American whites - A tale of two loci

Objective, To better understand genetic contributions to autoimmunity, immu nogenetic markers were studied in two racially discrete and geographically isolated populations of patients with idiopathic inflammatory myopathy (IIM ), Methods, Clinical characteristics, as well as clinical and autoantibody sub sets, were defined in 151 American white patients and 50 Korean patients wi th IIM, HLA-DRB1 and DQA1 genotyping was performed on patients and racially matched controls by standard molecular techniques. Gm allotypes and phenot ypes were determined by the hemagglutination-inhibition method, Results. HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles shari ng the first hypervariable region motif (EYSTS13)-E-9 were major genetic ri sk factors for the development of myositis in whites (corrected P [P-corr] < 0.0004, odds ratio [OR] 11.2, 4.5, and 3.1, respectively, for each factor versus controls). Although both the white and Korean patients had a simila r distribution of clinical characteristics, autoantibody profiles, and clin ical groups, no HLA-DRB1 nor DQA1 allele or motif was found to be a risk fa ctor for IIM in the Korean patients. However, DRB1*14 was a protective fact or in Korean patients without myositis-specific autoantibodies (P-corr = 0. 004, OR 0.046), In addition, although no Gm phenotype or allotype was ident ified as a risk factor in whites, Gm 21 was a protective factor for the dev elopment of IIM in Koreans (P-corr = 0.024, OR 0.3), Conclusion. Although myositis patients in the US and Korea share similar cl inical and serologic features, the immune response genes predisposing to an d protecting from myositis in each of these ethnic groups differ at two chr omosomal loci. These data suggest that multiple genetic loci should be stud ied to identify risk and protective factors for some autoimmune diseases in various ethnic populations.