PLoS ONE (Jan 2014)

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB1*13:02 and *14:03.

  • Hiroshi Furukawa,
  • Aya Kawasaki,
  • Shomi Oka,
  • Ikue Ito,
  • Kota Shimada,
  • Shoji Sugii,
  • Atsushi Hashimoto,
  • Akiko Komiya,
  • Naoshi Fukui,
  • Yuya Kondo,
  • Satoshi Ito,
  • Taichi Hayashi,
  • Isao Matsumoto,
  • Makio Kusaoi,
  • Hirofumi Amano,
  • Tatsuo Nagai,
  • Shunsei Hirohata,
  • Keigo Setoguchi,
  • Hajime Kono,
  • Akira Okamoto,
  • Noriyuki Chiba,
  • Eiichi Suematsu,
  • Masao Katayama,
  • Kiyoshi Migita,
  • Akiko Suda,
  • Shigeru Ohno,
  • Hiroshi Hashimoto,
  • Yoshinari Takasaki,
  • Takayuki Sumida,
  • Shouhei Nagaoka,
  • Naoyuki Tsuchiya,
  • Shigeto Tohma

DOI
https://doi.org/10.1371/journal.pone.0087792
Journal volume & issue
Vol. 9, no. 2
p. e87792

Abstract

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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.