Affordable Access

Access to the full text

Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still’s disease

Authors
  • Asano, Tomoyuki1
  • Furukawa, Hiroshi2
  • Sato, Shuzo1
  • Yashiro, Makiko1
  • Kobayashi, Hiroko1
  • Watanabe, Hiroshi1
  • Suzuki, Eiji3
  • Ito, Tomoyuki4
  • Ubara, Yoshifumi5
  • Kobayashi, Daisuke6
  • Iwanaga, Nozomi7
  • Izumi, Yasumori7
  • Fujikawa, Keita8
  • Yamasaki, Satoshi9
  • Nakamura, Tadashi10
  • Koga, Tomohiro11
  • Shimizu, Toshimasa11
  • Umeda, Masataka11
  • Nonaka, Fumiaki12
  • Yasunami, Michio13
  • And 8 more
  • 1 Fukushima Medical University School of Medicine, Department of Rheumatology, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan , Fukushima (Japan)
  • 2 University of Tsukuba, Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan , Tsukuba (Japan)
  • 3 Ohta Nishinouchi General Hospital Foundation, Department of Rheumatology, 2-5-20 Nishinouchi, Koriyama, Fukushima, 963-8558, Japan , Koriyama (Japan)
  • 4 Department of Rheumatology Nagaoka Red Cross Hospital, 297-1, Senshu-2, Nagaoka, Niigata, 940-2085, Japan , Nagaoka (Japan)
  • 5 Toranomon Hospital, Department of Rheumatology, Toranomon 2-2-2, Minato-ku, Tokyo, 105-8470, Japan , Minato-ku (Japan)
  • 6 Niigata Rheumatic Center, Department of Rheumatology, 1-2-8 Honcho, Shibata, Niigata, 957-0054, Japan , Shibata (Japan)
  • 7 Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan , Omura (Japan)
  • 8 Isahaya General Hospital, Department of Rheumatology, Japan Community Health care Organization, Eishohigashi-machi 24-1, Isahaya, 854-8501, Japan , Isahaya (Japan)
  • 9 Kurume University Medical Center, Department of Rheumatology, Kokubu 155-1 1-2-3, Kurume, 734-8551, Japan , Kurume (Japan)
  • 10 Sakurajyuji Hospital, Department of Rheumatology, Miyukibe 1-1-1, Kumamoto, 861-4173, Japan , Kumamoto (Japan)
  • 11 Nagasaki University, Department of Immunology and Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Sakamoto1-7-1, Nagasaki, 852-8501, Japan , Nagasaki (Japan)
  • 12 Sasebo City General Hospital, Departments of Rheumatology, Hirase 9-3, Sasebo, 857-8511, Japan , Sasebo (Japan)
  • 13 Saga-ken Medical Centre Koseikan, Department of Medical Genomics, Life Science Institute, 400 Kasemachi-Nakabaru, Saga, 840-8571, Japan , Saga (Japan)
  • 14 Sasebo Chuo Hospital, Department of Rheumatology, Yamato 15, Sasebo, 857-1195, Japan , Sasebo (Japan)
  • 15 National Hospital Organization Sagamihara National Hospital, Clinical Research Center for Allergy and Rheumatology, 18-1 Sakuradai, Minami-ku, Sagamihara, 252-0392, Japan , Minami-ku (Japan)
  • 16 Nagasaki University, Department of Human Genetics, Atomic Bomb Disease Institute, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan , Nagasaki (Japan)
  • 17 Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan , Fukushima (Japan)
Type
Published Article
Journal
Arthritis Research & Therapy
Publisher
Springer Science and Business Media LLC
Publication Date
Sep 12, 2017
Volume
19
Issue
1
Identifiers
DOI: 10.1186/s13075-017-1406-x
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundHLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still’s disease (AOSD) in a Japanese population by determining the DRB1 allele distributions.MethodsDRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing.ResultsIn Japanese patients with AOSD, we observed a predisposing association of DRB1*15:01 (p = 8.60 × 10−6, corrected p (Pc) = 0.0002, odds ratio (OR) = 3.04, 95% confidence interval (95% CI) = 1.91–4.84) and DR5 serological group (p = 0.0006, OR = 2.39, 95% CI = 1.49–3.83) and a protective association of DRB1*09:01 (p = 0.0004, Pc = 0.0110, OR = 0.34, 95% CI = 0.18–0.66) with AOSD, and amino acid residues 86 and 98 of the DRβ chain were protectively associated with AOSD. MEFV variants were identified in 49 patients with AOSD (56.3%). The predisposing effect of DR5 was confirmed only in patients with AOSD who had MEFV variants and not in those without MEFV variants. Additionally, DR5 in patients with AOSD are associated with macrophage activation syndrome (MAS) and steroid pulse therapy.ConclusionThe DRB1*15:01 and DR5 are both associated with AOSD susceptibility in Japanese subjects. A protective association between the DRB1*09:01 allele and AOSD was also observed in these patients. Our data also highlight the effects of DRB1 alleles in susceptibility to AOSD.

Report this publication

Statistics

Seen <100 times