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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Tomoyuki Asano, Hiroshi Furukawa, Shuzo Sato, Makiko Yashiro, Hiroko Kobayashi, Hiroshi Watanabe, Eiji Suzuki, Tomoyuki Ito, Yoshifumi Ubara, Daisuke Kobayashi, Nozomi Iwanaga, Yasumori Izumi, Keita Fujikawa, Satoshi Yamasaki, Tadashi Nakamura, Tomohiro Koga, Toshimasa Shimizu, Masataka Umeda, Fumiaki Nonaka, Michio Yasunami, Yukitaka Ueki, Katsumi Eguchi, Naoyuki Tsuchiya, Shigeto Tohma, Koh-ichiro Yoshiura, Hiromasa Ohira, Atsushi Kawakami, Kiyoshi Migita

ABSTRACT

BACKGROUND: HLA-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. METHODS: DRB1 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. RESULTS: In 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. CONCLUSION: The 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. More... »

PAGES

199

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-017-1406-x

DOI

http://dx.doi.org/10.1186/s13075-017-1406-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091609767

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28899403


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445 schema:name Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Fukushima, Japan
446 Department of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, 960-1295, Fukushima, Fukushima, Japan
447 rdf:type schema:Organization
448 https://www.grid.ac/institutes/grid.415288.2 schema:alternateName Sasebo City General Hospital
449 schema:name Departments of Rheumatology, Sasebo City General Hospital, Hirase 9-3, 857-8511, Sasebo, Japan
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451 https://www.grid.ac/institutes/grid.415689.7 schema:alternateName National Sagamihara Hospital
452 schema:name Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, 252-0392, Minami-ku, Sagamihara, Japan
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454 https://www.grid.ac/institutes/grid.416533.6 schema:alternateName Saga-Ken Medical Centre Koseikan
455 schema:name Department of Medical Genomics, Life Science Institute, Saga-ken Medical Centre Koseikan, 400 Kasemachi-Nakabaru, 840-8571, Saga, Japan
456 rdf:type schema:Organization
457 https://www.grid.ac/institutes/grid.470128.8 schema:alternateName Kurume University Medical Center
458 schema:name Department of Rheumatology, Kurume University Medical Center, Kokubu 155-1 1-2-3, 734-8551, Kurume, Japan
459 rdf:type schema:Organization
 




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