Abstract
Many studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic lupus erythematosus (SLE) have been performed. However, few protective associations with HLA-DRB1 alleles have been reported. Here, we sought protective, as well as predispositional, alleles of HLA-DRB1 in Japanese SLE patients. An association study was conducted for HLA-DRB1 in Japanese SLE patients. Relative predispositional effects were analyzed by sequential elimination of carriers of each allele with the strongest association. We also explored the association of DRB1 alleles with SLE phenotypes including the presence of autoantibody and clinical manifestations. Significantly different carrier frequencies of certain DRB1 alleles were found to be associated with SLE as follows: increased DRB1*15:01 (P = 5.48×10−10, corrected P (Pc) = 1.59×10−8, odds ratio [OR] 2.17, 95% confidence interval [CI] 1.69–2.79), decreased DRB1*13:02 (P = 7.17×10−5, Pc = 0.0020, OR 0.46, 95% CI 0.34–0.63) and decreased DRB1*14:03 (P = 0.0010, Pc = 0.0272, OR 0.34, 95% CI 0.18–0.63). Additionally, the “*15:01/*13:02 or *14:03” genotype tended to be negatively associated with SLE (P = 0.4209, OR 0.66), despite there being significant positive associations with *15:01 when present together with alleles other than *13:02 or *14:03 (P = 1.79×10−11, OR 2.39, 95% CI 1.84–3.10). This protective effect of *13:02 and *14:03 was also confirmed in SLE patients with different clinical phenotypes. To the best of our knowledge, this is the first report of a protective association between the carrier frequencies of HLA-DRB1*13:02 and *14:03 and SLE in the Japanese population.
Highlights
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease of unknown etiology that affects multiple organs and is associated with the production of several different autoantibodies
human leukocyte antigen (HLA)-DRB1 and DQB1 genotyping was performed in 459 SLE patients and 307 healthy controls in the first set to compare carrier frequencies of each allele or haplotype (Table 1, left column, Table S1)
The positive association between the carrier frequency of DRB1*15:01 and SLE failed to reach significance in this set (Pc = 0.0705, odds ratio [OR] 1.76, 95% confidence interval [CI] 1.22–2.53, Table 1), a significant protective association was found for DRB1*13:02 and SLE (Pc = 0.0123, OR 0.42, 95% CI 0.26–0.68)
Summary
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease of unknown etiology that affects multiple organs and is associated with the production of several different autoantibodies. It is a systemic inflammatory disease susceptibility to which is associated with genetic and environmental factors [1]. Only limited information is available concerning protective DRB1 alleles for SLE, i.e. those with a reduced frequency in patients. We explored associations of DRB1 alleles with SLE phenotypes including the presence of autoantibody and clinical manifestations of disease
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