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RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis

Oka, A; Asano, Y; Hasegawa, M; Fujimoto, M; Ishikawa, O; Kuwana, M; Kawaguchi, Y; ... Ihn, H; + view all (2017) RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis. Journal of Investigative Dermatology , 137 (9) pp. 1878-1886. 10.1016/j.jid.2017.04.028. Green open access

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Abstract

Systemic sclerosis (SSc) is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen (HLA) locus. However, the functional relationship between HLA gene(s) and disease development remains unknown. To elucidate major histocompatibility complex (MHC)-linked SSc genetics, we performed genotyping of MHC-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 2 MHC haplotypes associated with SSc. Exome sequencing and targeted analysis of these risk haplotypes identified rs17847931 in retinoid X receptor beta (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 SSc. Furthermore, the number of risk factors was shown to be a predominant factor, as individuals with 2 factors had elevated risk (P=6.7 × 10(-13); OR=30.2). We concluded that RXRB may be involved in anti-fibrotic activity in skin and chromatin remodeling.

Type: Article
Title: RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jid.2017.04.028
Publisher version: https://doi.org/10.1016/j.jid.2017.04.028
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1556981
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