Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese populations

Hiroshi Furukawa; Shomi Oka; Kota Shimada; Atsushi Hashimoto; Akiko Komiya; Shinichiro Tsunoda; Akiko Suda; Satoshi Ito; Koichiro Saisho; Masao Katayama; Satoshi Shinohara; Takeo Sato; Katsuya Nagatani; Seiji Minota; Toshihiro Matsui; Naoshi Fukui; Shoji Sugii; Hajime Sano; Kiyoshi Migita; Shouhei Nagaoka; Shigeto Tohma

doi:10.1371/journal.pone.0204459

Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese populations

PLoS One. 2018 Sep 20;13(9):e0204459. doi: 10.1371/journal.pone.0204459. eCollection 2018.

Authors

Hiroshi Furukawa^{1

2}, Shomi Oka^{1

2}, Kota Shimada^{3

4}, Atsushi Hashimoto³, Akiko Komiya¹, Shinichiro Tsunoda^{5

6}, Akiko Suda⁷, Satoshi Ito⁸, Koichiro Saisho⁹, Masao Katayama¹⁰, Satoshi Shinohara¹¹, Takeo Sato¹², Katsuya Nagatani¹², Seiji Minota¹², Toshihiro Matsui¹, Naoshi Fukui¹, Shoji Sugii⁴, Hajime Sano⁵, Kiyoshi Migita^{13

14}, Shouhei Nagaoka⁷, Shigeto Tohma^{1

15}

Affiliations

¹ Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
² Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
³ Department of Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
⁴ Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan.
⁵ Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
⁶ Department of Rheumatology, Sumitomo Hospital, Osaka, Japan.
⁷ Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, Japan.
⁸ Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
⁹ Department of Orthopedics/Rheumatology, Miyakonojo Medical Center, National Hospital Organization, Miyakonojo, Japan.
¹⁰ Department of Internal Medicine, Nagoya Medical Center, National Hospital Organization, Nagoya, Japan.
¹¹ Tochigi Rheumatology Clinic, Utsunomiya, Japan.
¹² Division of Rheumatology and Clinical Immunology, Jichi Medical University, Shimotsuke, Japan.
¹³ Clinical Research Center, Nagasaki Medical Center, National Hospital Organization, Omura, Japan.
¹⁴ Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Japan.
¹⁵ Tokyo National Hospital, National Hospital Organization, Kiyose, Japan.

Abstract

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized with joint destructions; environmental and genetic factors were thought to be involved in the etiology of RA. The production of anti-citrullinated peptide antibodies (ACPA) is specifically associated with RA. DRB1 is associated with the susceptibility of RA, especially ACPA-positive RA [ACPA(+)RA]. However, a few studies reported on the independent associations of DPB1 alleles with RA susceptibility. Thus, we investigated the independent association of DPB1 alleles with RA in Japanese populations.

Methods: Association analyses of DPB1 were conducted by logistic regression analysis in 1667 RA patients and 413 controls.

Results: In unconditioned analysis, DPB1*04:02 was nominally associated with the susceptibility of ACPA(+)RA (P = 0.0021, corrected P (Pc) = 0.0275, odds ratio [OR] 1.52, 95% confidence interval [CI] 1.16-1.99). A significant association of DPB1*02:01 with the susceptibility of ACPA(+)RA was observed, when conditioned on DRB1 (Padjusted = 0.0003, Pcadjusted = 0.0040, ORadjusted 1.47, 95%CI 1.19-1.81). DPB1*05:01 was tended to be associated with the protection against ACPA(+)RA, when conditioned on DRB1 (Padjusted = 0.0091, Pcadjusted = 0.1184, ORadjusted 0.78, 95%CI 0.65-0.94). When conditioned on DRB1, the association of DPB1*04:02 with ACPA(+)RA was disappeared. No association of DPB1 alleles with ACPA-negative RA was detected.

Conclusion: The independent association of DPB1*02:01 with Japanese ACPA(+)RA was identified.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Arthritis, Rheumatoid / genetics*
Case-Control Studies
Female
Genotype
HLA-DP beta-Chains / genetics*
Humans
Japan
Male
Middle Aged

Substances

HLA-DP beta-Chains
HLA-DPB1 antigen

Grants and funding

The work was supported by Grants-in-Aid for Scientific Research (B, C) (26293123, 22591090, 15K09543, 18K08402) and for Young Scientists (B) (24791018) from the Japan Society for the Promotion of Science, Health and Labour Science Research Grants from the Ministry of Health, Labour, and Welfare of Japan, Grants-in-Aid of the Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from Japan Agency for Medical Research and Development, Grants-in-Aid for Clinical Research from National Hospital Organization, Research Grants from Daiwa Securities Health Foundation, Research Grants from Japan Research Foundation for Clinical Pharmacology, Research Grants from The Nakatomi Foundation, Research Grants from Takeda Science Foundation, Research Grants from Mitsui Sumitomo Insurance Welfare Foundation, Bristol-Myers K.K. RA Clinical Investigation Grant from Bristol-Myers Squibb Co., and research grants from the following pharmaceutical companies: Abbott Japan Co., Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsuibishi Tanabe Pharma Corporation, Merck Sharp and Dohme Inc., Pfizer Japan Inc., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. The funders had no role in study design, data collection and analysis, decision to publish, or preparing the manuscript.