Influence of Susceptible HLA-DRB1 Alleles on Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans

초록

Background/Purpose: We investigated the association between human leukocyte antigen (HLA)-DRB1 alleles and systemic lupus erythematosus (SLE) susceptibility and whether each allele has a significant effect on clinical manifestations and autoantibody profiles in a Korean population. Methods: All SLE patients (n=1,089) and control subjects (n=2,161) were Korean. We performed a two-stage analysis in a discovery set (group 1: 475 SLE and 1,119 controls) and a replication set (group 2: 614 SLE and 1,072 controls) using high-resolution HLA-DRB1 typing. The odds ratio (OR) of risk alleles associated with SLE was calculated by a regression method, which was adjusted for age, sex, and disease duration. Results: We found that four HLA-DRB1 alleles [two confirmed alleles; *15:01 (P=1.11×10-13), *09:01 (P=1.59×10-5), two novel alleles; *08:03 (P=8.80×10-8), *07:01 (P=1.14×10-6)] and were associated with susceptibility to SLE. Double copies of these risk alleles (OR 3.38) were associated with a higher risk of developing SLE than a single copy (OR 1.95), showing additive genetic effects. In addition, three novel HLA-DRB1*12:02 (P=6.35×10-4), *11:01 (P=1.24×10-3), *13:02 (P=8.88×10-3) alleles were significantly protective against SLE. The HLA-DRB1*15:01 allele alone (OR 2.20) and double-copies of risk alleles (OR 3.71) increased the risk for anti-Sm production. In addition, SLE patients with double-copies of risk alleles showed more diverse clinical manifestations. Conclusion: We demonstrated that four HLA–DRB1 risk alleles were associated with SLE in a Korean population, and also promote the production of anti-Sm and diverse clinical manifestations