PMID- 27116456
OWN - NLM
STAT- MEDLINE
DCOM- 20170320
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 4
DP  - 2016
TI  - Human Leukocyte Antigen and Systemic Sclerosis in Japanese: The Sign of the Four 
      Independent Protective Alleles, DRB1*13:02, DRB1*14:06, DQB1*03:01, and 
      DPB1*02:01.
PG  - e0154255
LID - 10.1371/journal.pone.0154255 [doi]
LID - e0154255
AB  - OBJECTIVE: Several studies on associations between human leukocyte antigen (HLA) 
      allele frequencies and susceptibility to systemic sclerosis (SSc) have been 
      reported. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies 
      (ATA) are found in SSc patients. Here, we sought to identify HLA alleles 
      associated with SSc in Japanese, and explored their associations with SSc 
      phenotypes including the presence of autoantibodies. METHODS: Associations of 
      HLA-DRB1, DQB1, and DPB1 were analyzed in 463 Japanese SSc patients and 413 
      controls. RESULTS: We found that DRB1*13:02 (P = 0.0011, Pc = 0.0319, odds ratio 
      [OR] 0.46, 95% confidence interval [CI] 0.29-0.73), DRB1*14:06 (P = 6.60X10-5, Pc 
      = 0.0020, OR 0.05, 95%CI 0.01-0.41), DQB1*03:01 (P = 0.0009, Pc = 0.0150, OR 
      0.56, 95%CI 0.40-0.79), and DPB1*02:01 (P = 5.16X10-6, Pc = 8.77X10-5, OR 0.52, 
      95%CI 0.39-0.69) were protectively associated with SSc. In addition, these four 
      alleles seemed to be independently associated with the protection against the 
      susceptibility of SSc. On the other hand, we could not find predisposing alleles 
      for overall SSc. With respect to SSc subsets, a tendency for these four alleles 
      to be protectively associated was observed. However, there was a significant 
      association between DRB1*01:01, DRB1*10:01, DQB1*05:01, and DPB1*04:02 and the 
      susceptibility to SSc with ACA. On the other hand, the presence of DRB1*15:02, 
      DQB1*06:01, DPB1*03:01, and DPB1*09:01 was associated with SSc with ATA. 
      CONCLUSION: Thus, the present study has identified protective associations of the 
      four HLA class II alleles with overall Japanese SSc and predisposing associations 
      of HLA class II alleles with Japanese SSc subsets.
FAU - Furukawa, Hiroshi
AU  - Furukawa H
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan.
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Japan.
FAU - Oka, Shomi
AU  - Oka S
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan.
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Japan.
FAU - Kawasaki, Aya
AU  - Kawasaki A
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan.
FAU - Shimada, Kota
AU  - Shimada K
AD  - Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, 
      18-1 Sakuradai, Minami-ku, Sagamihara, Japan.
AD  - Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, 2-8-29 
      Musashi-dai, Fuchu, Japan.
FAU - Sugii, Shoji
AU  - Sugii S
AD  - Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, 2-8-29 
      Musashi-dai, Fuchu, Japan.
FAU - Matsushita, Takashi
AU  - Matsushita T
AD  - Department of Dermatology, Faculty of Medicine, Institute of Medical, 
      Pharmaceutical, and Health Sciences, Kanazawa University, 13-1 Takaramachi, 
      Kanazawa, Japan.
FAU - Hashimoto, Atsushi
AU  - Hashimoto A
AD  - Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, 
      18-1 Sakuradai, Minami-ku, Sagamihara, Japan.
FAU - Komiya, Akiko
AU  - Komiya A
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Japan.
FAU - Fukui, Naoshi
AU  - Fukui N
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Japan.
FAU - Kobayashi, Kouji
AU  - Kobayashi K
AD  - Department of Rheumatology, Yokohama Minami Kyosai Hospital, 1-21-1 
      Rokuura-higashi, Kanazawa-ku, Yokohama, Japan.
FAU - Osada, Atsumu
AU  - Osada A
AD  - Department of Rheumatology, Yokohama Minami Kyosai Hospital, 1-21-1 
      Rokuura-higashi, Kanazawa-ku, Yokohama, Japan.
FAU - Ihata, Atsushi
AU  - Ihata A
AD  - Department of Rheumatology, Yokohama Minami Kyosai Hospital, 1-21-1 
      Rokuura-higashi, Kanazawa-ku, Yokohama, Japan.
FAU - Kondo, Yuya
AU  - Kondo Y
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 
      1-1-1 Tennodai, Tsukuba, Japan.
FAU - Nagai, Tatsuo
AU  - Nagai T
AD  - Department of Rheumatology and Infectious Diseases, Kitasato University School of 
      Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Japan.
FAU - Setoguchi, Keigo
AU  - Setoguchi K
AD  - Department of Allergy and Immunological Diseases, Tokyo Metropolitan Cancer and 
      Infectious Diseases Center Komagome Hospital, 3-18-22 Hon-komagome, Bunkyo-ku, 
      Tokyo, Japan.
FAU - Okamoto, Akiko
AU  - Okamoto A
AD  - Department of Internal Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, 
      Tokyo, Japan.
FAU - Okamoto, Akira
AU  - Okamoto A
AD  - Department of Rheumatology, Himeji Medical Center, National Hospital 
      Organization, 68 Hon-machi, Himeji, Japan.
FAU - Chiba, Noriyuki
AU  - Chiba N
AD  - Department of Rheumatology, Morioka Hospital, National Hospital Organization, 
      1-25-1 Aoyama, Morioka, Japan.
FAU - Suematsu, Eiichi
AU  - Suematsu E
AD  - Department of Internal Medicine and Rheumatology, Clinical Research Institute, 
      Kyushu Medical Center, National Hospital Organization, 1-8-1 Jigyohama, Chuo-ku, 
      Fukuoka, Japan.
FAU - Kono, Hajime
AU  - Kono H
AD  - Department of Internal Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, 
      Tokyo, Japan.
FAU - Katayama, Masao
AU  - Katayama M
AD  - Department of Internal Medicine, Nagoya Medical Center, National Hospital 
      Organization, 4-1-1 Sannomaru, Naka-ku, Nagoya, Japan.
FAU - Hirohata, Shunsei
AU  - Hirohata S
AD  - Department of Rheumatology and Infectious Diseases, Kitasato University School of 
      Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Japan.
FAU - Sumida, Takayuki
AU  - Sumida T
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 
      1-1-1 Tennodai, Tsukuba, Japan.
FAU - Migita, Kiyoshi
AU  - Migita K
AD  - Clinical Research Center, Nagasaki Medical Center, National Hospital 
      Organization, 2-1001-1 Kubara, Omura, Japan.
FAU - Hasegawa, Minoru
AU  - Hasegawa M
AD  - Department of Dermatology, School of Medicine, Faculty of Medical Sciences, 
      University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji, Japan.
FAU - Fujimoto, Manabu
AU  - Fujimoto M
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1 
      Tennodai, Tsukuba, Japan.
FAU - Sato, Shinichi
AU  - Sato S
AD  - Department of Dermatology, Graduate School of Medicine, University of Tokyo, 
      7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
FAU - Nagaoka, Shouhei
AU  - Nagaoka S
AD  - Department of Rheumatology, Yokohama Minami Kyosai Hospital, 1-21-1 
      Rokuura-higashi, Kanazawa-ku, Yokohama, Japan.
FAU - Takehara, Kazuhiko
AU  - Takehara K
AD  - Department of Dermatology, Faculty of Medicine, Institute of Medical, 
      Pharmaceutical, and Health Sciences, Kanazawa University, 13-1 Takaramachi, 
      Kanazawa, Japan.
FAU - Tohma, Shigeto
AU  - Tohma S
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara, Japan.
FAU - Tsuchiya, Naoyuki
AU  - Tsuchiya N
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160426
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPB1*02:01 antigen)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*13 antigen)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Asian People/genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HLA-DP beta-Chains/*genetics
MH  - HLA-DQ beta-Chains/*genetics
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Japan/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Protective Factors
MH  - Scleroderma, Systemic/epidemiology/*genetics
PMC - PMC4846066
COIS- Competing Interests: HF has the following conflicts, and the following funders 
      are supported wholly or in part by the indicated pharmaceutical companies. The 
      Japan Research Foundation for Clinical Pharmacology is run by Daiichi Sankyo, the 
      Takeda Science Foundation is supported by an endowment from Takeda Pharmaceutical 
      Company and the Nakatomi Foundation was established by Hisamitsu Pharmaceutical 
      Co., Inc. The Daiwa Securities Health Foundation was established by Daiwa 
      Securities Group Inc. and Mitsui Sumitomo Insurance Welfare Foundation was 
      established by Mitsui Sumitomo Insurance Co., Ltd. HF received honoraria from 
      Ajinomoto Co., Inc., Daiichi Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., 
      Ltd., Pfizer Japan Inc., and Takeda Pharmaceutical Company. ST was supported by 
      research grants from 9 pharmaceutical companies: Abbott Japan Co., Ltd., Astellas 
      Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe 
      Pharma Corporation, Merck Sharp and Dohme Inc., Pfizer Japan Inc., Takeda 
      Pharmaceutical Company Limited, Teijin Pharma Limited. ST received honoraria from 
      Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK., Chugai 
      Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma 
      Corporation, Pfizer Japan Inc. The other authors declare no financial or 
      commercial conflict of interest. This does not alter our adherence to PLOS ONE 
      policies on sharing data and materials.
EDAT- 2016/04/27 06:00
MHDA- 2017/03/21 06:00
PMCR- 2016/04/26
CRDT- 2016/04/27 06:00
PHST- 2015/12/27 00:00 [received]
PHST- 2016/04/11 00:00 [accepted]
PHST- 2016/04/27 06:00 [entrez]
PHST- 2016/04/27 06:00 [pubmed]
PHST- 2017/03/21 06:00 [medline]
PHST- 2016/04/26 00:00 [pmc-release]
AID - PONE-D-15-55905 [pii]
AID - 10.1371/journal.pone.0154255 [doi]
PST - epublish
SO  - PLoS One. 2016 Apr 26;11(4):e0154255. doi: 10.1371/journal.pone.0154255. 
      eCollection 2016.