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RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I Antibody-Positive Systemic Sclerosis.
Oka, Akira; Asano, Yoshihide; Hasegawa, Minoru; Fujimoto, Manabu; Ishikawa, Osamu; Kuwana, Masataka; Kawaguchi, Yasushi; Yamamoto, Toshiyuki; Takahashi, Hiroki; Goto, Daisuke; Endo, Hirahito; Jinnin, Masatoshi; Mano, Shuhei; Hosomichi, Kazuyoshi; Mabuchi, Tomotaka; Ueda, Mahoko Takahashi; Nakagawa, So; Beck, Stephan; Bahram, Seiamak; Takehara, Kazuhiko; Sato, Shinichi; Ihn, Hironobu.
Afiliación
  • Oka A; The Institute of Medical Science, Tokai University, Kanagawa, Japan. Electronic address: oka246@is.icc.u-tokai.ac.jp.
  • Asano Y; Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
  • Hasegawa M; Department of Dermatology, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
  • Fujimoto M; Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
  • Ishikawa O; Department of Dermatology, Gunma University Graduate School of Medicine, Gunma, Japan.
  • Kuwana M; Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
  • Kawaguchi Y; Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
  • Yamamoto T; Department of Dermatology, Fukushima Medical University, Fukushima, Japan.
  • Takahashi H; Department of Rheumatology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
  • Goto D; Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
  • Endo H; Department of Rheumatology, Jusendo General Hospital, Fukushima, Japan.
  • Jinnin M; Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Mano S; Department of Mathematical Analysis and Statistical Inference, The Institute of Statistical Mathematics, Tokyo, Japan.
  • Hosomichi K; Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Mabuchi T; Department of Dermatology, Tokai University School of Medicine, Kanagawa, Japan.
  • Ueda MT; Micro/Nano Technology Center, Tokai University, Kanagawa, Japan.
  • Nakagawa S; Micro/Nano Technology Center, Tokai University, Kanagawa, Japan; Department of Molecular Life Sciences, Tokai University School of Medicine, Kanagawa, Japan.
  • Beck S; Medical Genomics, UCL Cancer Institute, University College London, London, UK.
  • Bahram S; INSERM UMR_S 1109, LabEx Transplantex, LIA France-Japan FJ-HLA, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Strasbourg, France.
  • Takehara K; Department of Molecular Pathology of Skin, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
  • Sato S; Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
  • Ihn H; Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
J Invest Dermatol ; 137(9): 1878-1886, 2017 09.
Article en En | MEDLINE | ID: mdl-28506627
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / ADN-Topoisomerasas de Tipo I / Predisposición Genética a la Enfermedad / Cadenas beta de HLA-DP Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Invest Dermatol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / ADN-Topoisomerasas de Tipo I / Predisposición Genética a la Enfermedad / Cadenas beta de HLA-DP Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Invest Dermatol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos