RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I Antibody-Positive Systemic Sclerosis

Akira Oka, Yoshihide Asano, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Masataka Kuwana, Yasushi Kawaguchi, Toshiyuki Yamamoto, Hiroki Takahashi, Daisuke Goto, Hirahito Endo, Masatoshi Jinnin, Shuhei Mano, Kazuyoshi Hosomichi, Tomotaka Mabuchi, Mahoko Takahashi Ueda, So Nakagawa, Stephan Beck, Seiamak Bahram, Kazuhiko TakeharaShinichi Sato, Hironobu Ihn

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Systemic sclerosis is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen locus. However, the functional relationship between human leukocyte antigen gene(s) and disease development remains unknown. To elucidate major histocompatibility complex-linked systemic sclerosis genetics, we performed genotyping of major histocompatibility complex-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed two major histocompatibility complex haplotypes associated with systemic sclerosis. Exome sequencing and targeted analysis of these risk haplotypes identified rs17847931 in RXRB as a susceptibility variant (P = 1.3 × 10−15; odds ratio [OR] = 9.4) with amino acid substitution p.V95A on the risk haplotype harboring HLA-DPB1∗13:01. No identical variant in the other haplotype including DPB1*09:01 was observed, though that haplotype also showed a significant association (P = 8.5 × 10−22; OR = 4.3) with systemic sclerosis. Furthermore, the number of risk factors was shown to be a predominant factor, as individuals with two factors had elevated risk (P = 6.7 × 10−13; OR = 30.2). We concluded that RXRB may be involved in antifibrotic activity in skin and chromatin remodeling.

Original languageEnglish
Pages (from-to)1878-1886
Number of pages9
JournalJournal of Investigative Dermatology
Issue number9
Publication statusPublished - 2017 Sept
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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