PMID- 24498373
OWN - NLM
STAT- MEDLINE
DCOM- 20141020
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 2
DP  - 2014
TI  - Human leukocyte antigens and systemic lupus erythematosus: a protective role for 
      the HLA-DR6 alleles DRB1*13:02 and *14:03.
PG  - e87792
LID - 10.1371/journal.pone.0087792 [doi]
LID - e87792
AB  - Many studies on associations between human leukocyte antigen (HLA) allele 
      frequencies and susceptibility to systemic lupus erythematosus (SLE) have been 
      performed. However, few protective associations with HLA-DRB1 alleles have been 
      reported. Here, we sought protective, as well as predispositional, alleles of 
      HLA-DRB1 in Japanese SLE patients. An association study was conducted for 
      HLA-DRB1 in Japanese SLE patients. Relative predispositional effects were 
      analyzed by sequential elimination of carriers of each allele with the strongest 
      association. We also explored the association of DRB1 alleles with SLE phenotypes 
      including the presence of autoantibody and clinical manifestations. Significantly 
      different carrier frequencies of certain DRB1 alleles were found to be associated 
      with SLE as follows: increased DRB1*15:01 (P = 5.48x10(-)(1)(0), corrected P 
      (Pc) = 1.59x10(-)(8), odds ratio [OR] 2.17, 95% confidence interval [CI] 1.69-2.79), 
      decreased DRB1*13:02 (P = 7.17x10(-)(5), Pc = 0.0020, OR 0.46, 95% CI 0.34-0.63) and 
      decreased DRB1*14:03 (P = 0.0010, Pc = 0.0272, OR 0.34, 95% CI 0.18-0.63). 
      Additionally, the "*15:01/*13:02 or *14:03" genotype tended to be negatively 
      associated with SLE (P = 0.4209, OR 0.66), despite there being significant 
      positive associations with *15:01 when present together with alleles other than 
      *13:02 or *14:03 (P = 1.79x10(-)(1)(1), OR 2.39, 95% CI 1.84-3.10). This protective 
      effect of *13:02 and *14:03 was also confirmed in SLE patients with different 
      clinical phenotypes. To the best of our knowledge, this is the first report of a 
      protective association between the carrier frequencies of HLA-DRB1*13:02 and 
      *14:03 and SLE in the Japanese population.
FAU - Furukawa, Hiroshi
AU  - Furukawa H
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, Sagamihara, Japan.
FAU - Kawasaki, Aya
AU  - Kawasaki A
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba, Japan.
FAU - Oka, Shomi
AU  - Oka S
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, Sagamihara, Japan.
FAU - Ito, Ikue
AU  - Ito I
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba, Japan.
FAU - Shimada, Kota
AU  - Shimada K
AD  - Department of Rheumatology, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan 
      ; Department of Rheumatology, Sagamihara Hospital, National Hospital 
      Organization, Sagamihara, Japan.
FAU - Sugii, Shoji
AU  - Sugii S
AD  - Department of Rheumatology, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan.
FAU - Hashimoto, Atsushi
AU  - Hashimoto A
AD  - Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, 
      Sagamihara, Japan.
FAU - Komiya, Akiko
AU  - Komiya A
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, Sagamihara, Japan.
FAU - Fukui, Naoshi
AU  - Fukui N
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, Sagamihara, Japan.
FAU - Kondo, Yuya
AU  - Kondo Y
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 
      Tsukuba, Japan.
FAU - Ito, Satoshi
AU  - Ito S
AD  - Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
FAU - Hayashi, Taichi
AU  - Hayashi T
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 
      Tsukuba, Japan.
FAU - Matsumoto, Isao
AU  - Matsumoto I
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 
      Tsukuba, Japan.
FAU - Kusaoi, Makio
AU  - Kusaoi M
AD  - Department of Internal Medicine and Rheumatology, Juntendo University School of 
      Medicine, Tokyo, Japan.
FAU - Amano, Hirofumi
AU  - Amano H
AD  - Department of Internal Medicine and Rheumatology, Juntendo University School of 
      Medicine, Tokyo, Japan.
FAU - Nagai, Tatsuo
AU  - Nagai T
AD  - Department of Rheumatology and Infectious Disease, Kitasato University School of 
      Medicine, Sagamihara, Japan.
FAU - Hirohata, Shunsei
AU  - Hirohata S
AD  - Department of Rheumatology and Infectious Disease, Kitasato University School of 
      Medicine, Sagamihara, Japan.
FAU - Setoguchi, Keigo
AU  - Setoguchi K
AD  - Department of Allergy and Immunological Diseases, Tokyo Metropolitan Cancer and 
      Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
FAU - Kono, Hajime
AU  - Kono H
AD  - Department of Internal Medicine, Teikyo University, Tokyo, Japan.
FAU - Okamoto, Akira
AU  - Okamoto A
AD  - Department of Rheumatology, Himeji Medical Center, National Hospital 
      Organization, Himeji, Japan.
FAU - Chiba, Noriyuki
AU  - Chiba N
AD  - Department of Rheumatology, Morioka Hospital, National Hospital Organization, 
      Morioka, Japan.
FAU - Suematsu, Eiichi
AU  - Suematsu E
AD  - Department of Internal Medicine and Rheumatology, Clinical Research Institute, 
      Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan.
FAU - Katayama, Masao
AU  - Katayama M
AD  - Department of Internal Medicine, Nagoya Medical Center, National Hospital 
      Organization, Nagoya, Japan.
FAU - Migita, Kiyoshi
AU  - Migita K
AD  - Clinical Research Center, Nagasaki Medical Center, National Hospital 
      Organization, Omura, Japan.
FAU - Suda, Akiko
AU  - Suda A
AD  - Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, 
      Japan ; Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, 
      Japan.
FAU - Ohno, Shigeru
AU  - Ohno S
AD  - Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, 
      Japan.
FAU - Hashimoto, Hiroshi
AU  - Hashimoto H
AD  - Juntendo University School of Medicine, Tokyo, Japan.
FAU - Takasaki, Yoshinari
AU  - Takasaki Y
AD  - Department of Internal Medicine and Rheumatology, Juntendo University School of 
      Medicine, Tokyo, Japan.
FAU - Sumida, Takayuki
AU  - Sumida T
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 
      Tsukuba, Japan.
FAU - Nagaoka, Shouhei
AU  - Nagaoka S
AD  - Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, Japan.
FAU - Tsuchiya, Naoyuki
AU  - Tsuchiya N
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba, Japan.
FAU - Tohma, Shigeto
AU  - Tohma S
AD  - Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, 
      National Hospital Organization, Sagamihara, Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140203
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DR6 Antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Asian People/*genetics
MH  - Case-Control Studies
MH  - DNA/analysis
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-DR6 Antigen/*genetics/immunology
MH  - HLA-DRB1 Chains/*genetics/immunology
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*genetics/*immunology/prevention & control
MH  - Male
MH  - Middle Aged
MH  - Odds Ratio
MH  - Polymerase Chain Reaction
PMC - PMC3912000
COIS- Competing Interests: The following funders are supported in whole 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. AH was supported by research grants from Mitsubishi Tanabe 
      Pharma Corporation. NT is supported by SENSHIN Medical Research Foundation, which 
      is supported by an endowment from Mitsubishi Tanabe Pharma Corporation. 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. The other 
      authors declare no financial or commercial conflict of interest. This does not 
      alter the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials.
EDAT- 2014/02/06 06:00
MHDA- 2014/10/21 06:00
PMCR- 2014/02/03
CRDT- 2014/02/06 06:00
PHST- 2013/10/12 00:00 [received]
PHST- 2014/01/02 00:00 [accepted]
PHST- 2014/02/06 06:00 [entrez]
PHST- 2014/02/06 06:00 [pubmed]
PHST- 2014/10/21 06:00 [medline]
PHST- 2014/02/03 00:00 [pmc-release]
AID - PONE-D-13-41892 [pii]
AID - 10.1371/journal.pone.0087792 [doi]
PST - epublish
SO  - PLoS One. 2014 Feb 3;9(2):e87792. doi: 10.1371/journal.pone.0087792. eCollection 
      2014.