A large-scale association study identified multiple HLA-DRB1 alleles associated with ACPA-negative rheumatoid arthritis in Japanese subjects.

• Terao, Chikashi

• 大村, 浩一郎

• Kochi, Yuta

• Ikari, Katsunori

• Maruya, Etsuko

• Katayama, Masaki

• Shimada, Kota

• Murasawa, Akira

• Honjo, Shigeru

• Takasugi, Kiyoshi

• Matsuo, Keitaro

• Tajima, Kazuo

• Suzuki, Akari

• Yamamoto, Kazuhiko

• Momohara, Shigeki

• Yamanaka, Hisashi

• Yamada, Ryo

• Saji, Hiroo

• Matsuda, Fumihiko

• Mimori, Tsuneyo

抄録

[Background] HLA-DRB1 is associated with rheumatoid arthritis (RA). However, it has recently been suggested that HLA-DRB1 is only associated with patients with RA who have anticitrullinated peptide/protein antibodies (ACPA), which are specific to RA. [Objective] To elucidate whether specific HLA-DR alleles are associated with ACPA-negative RA development. [Methods] HLA-DRB1 typing was carried out in 368 Japanese ACPA-negative patients with RA and 1508 healthy volunteers as the first set, followed by HLA-DRB1 typing of 501 cases and 500 controls as the second set. The HLA-DRB1 allele frequency and diplotype frequency were compared in each group, and the results of the two studies were combined to detect HLA-DRB1 alleles or diplotypes associated with ACPA-negative RA. [Results] HLA-DRB1*12:01 was identified as a novel susceptibility allele for ACPA-negative RA (p=0.000088, OR=1.72, 95% CI 1.31 to 2.26). HLA-DRB1*04:05 and *14:03 showed moderate associations with ACPA-negative RA (p=0.0063, OR=1.26, 95% CI 1.07 to 1.49 and p=0.0043, OR=1.81, 95% CI 1.20 to 2.73, respectively). The shared epitope was weakly associated with ACPA-negative RA, but no dosage effect was detected (p=0.016, OR=1.17, 95% CI 1.03 to 1.34). A combination of HLA-DRB1*12:01 and DRB1*09:01 showed a strong association with susceptibility to ACPA-negative RA (p=0.00013, OR=3.62, 95% CI 1.79 to 7.30). Homozygosity for HLA-DR8 was significantly associated with ACPA-negative RA (p=0.0070, OR=2.16, 95% CI 1.22 to 3.82). It was also found that HLA-DRB1*15:02 and *13:02 were protective against ACPA-negative RA (p=0.00010, OR=0.68, 95% CI 0.56 to 0.83 and p=0.00059, OR=0.66, 95% CI 0.52 to 0.84, respectively). [Conclusions] In this large-scale association study multiple alleles and diplotypes were found to be associated with susceptibility to, or protection against, ACPA-negative RA.

収録刊行物

• Annals of the rheumatic diseases

  Annals of the rheumatic diseases 70 (12), 2134-2139, 2011-12

  BMJ Publishing Group Ltd & European League Against Rheumatism

キーワード

• Adult
• Aged
• Arthritis, Rheumatoid/genetics
• Autoantibodies/blood
• Case-Control Studies
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• HLA-DRB1 Chains/genetics
• Histocompatibility Testing/methods
• Humans
• Male
• Middle Aged
• Peptides, Cyclic/immunology

詳細情報

• CRID: 1050564285679738240
• NII論文ID: 120003796492
• NII書誌ID: AA00533085
• ISSN: 00034967
• HANDLE: 2433/152548
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles