PMID- 31770283
OWN - NLM
STAT- MEDLINE
DCOM- 20191206
LR  - 20221005
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 98
IP  - 48
DP  - 2019 Nov
TI  - Association of HLA-DRB1 genotype with younger age onset and elder age onset 
      rheumatoid arthritis in Japanese populations.
PG  - e18218
LID - 10.1097/MD.0000000000018218 [doi]
LID - e18218
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint 
      destructions and human leukocyte antigen (HLA)-DRB1 is an important genetic risk 
      factor for RA and influences the phenotype of RA. The clinical features of elder 
      age onset RA (EORA) were known to be different from those of younger age onset RA 
      (YORA). Previous studies reported the different association pattern of DRB1 
      alleles with YORA or EORA. The associations of DRB1 genotype with these RA 
      subsets remained almost unknown. We investigated the genotype association of DRB1 
      with YORA or EORA in Japanese populations.HLA genotyping was performed in 
      Japanese RA patients and the association of allele or genotype carrier 
      frequencies were analyzed.The genotype frequency of DRB104:05/DRB104:06 
      (P = .0204, OR 7.69, 95%CI 1.39-42.72), DRB104:05/DRB112:01 (P = .0050, OR 5.53, 
      95%CI 1.71-17.88), and DRB104:05/DRB115:01 (P = .0124, OR 3.34, 95%CI 1.39-8.02) 
      in YORA was higher than EORA. However, the frequencies of DRB101:01/DRB104:05 in 
      YORA was tended to be lower than EORA (P = .0784, OR 0.14, 95%CI 0.01-2.42). The 
      gene dosage effect of the shared epitope alleles was detected in EORA, but not in 
      YORA. Trans-complementing DQ heterodimer molecules, formed by DQA1 and DQB1 of 
      the haplotypes with and without shared epitope alleles, might explain the higher 
      genotype frequencies of "shared epitope /not shared epitope". Linear regression 
      analyses showed the primary role of DQB104:01 allele for the age at onset of 
      RA.This is the first report for the associations of DRB1 genotype with YORA or 
      EORA in the Japanese population and the differential distribution of the 
      genotypes was noted between these RA subsets. The involvement of DQ molecules for 
      the age at onset of RA was suggested.
FAU - Oka, Shomi
AU  - Oka S
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, Sagamihara.
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba.
AD  - Tokyo National Hospital, National Hospital Organization, Kiyose.
FAU - Furukawa, Hiroshi
AU  - Furukawa H
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, Sagamihara.
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba.
AD  - Tokyo National Hospital, National Hospital Organization, Kiyose.
FAU - Shimada, Kota
AU  - Shimada K
AD  - Department of Rheumatology, National Hospital Organization Sagamihara National 
      Hospital, Sagamihara.
AD  - Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Fuchu.
FAU - Hashimoto, Atsushi
AU  - Hashimoto A
AD  - Department of Rheumatology, National Hospital Organization Sagamihara National 
      Hospital, Sagamihara.
FAU - Komiya, Akiko
AU  - Komiya A
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, Sagamihara.
AD  - Department of Clinical Laboratory, National Hospital Organization Sagamihara 
      National Hospital, Sagamihara.
FAU - Tsunoda, Shinichiro
AU  - Tsunoda S
AD  - Division of Rheumatology, Department of Internal Medicine, Hyogo College of 
      Medicine, Nishinomiya.
AD  - Department of Rheumatology, Sumitomo Hospital, Osaka.
FAU - Saisho, Koichiro
AU  - Saisho K
AD  - Department of Orthopedics/Rheumatology, Miyakonojo Medical Center, National 
      Hospital Organization, Miyakonojo.
AD  - Tanimura Hospital, Nobeoka.
FAU - Tsuchiya, Naoyuki
AU  - Tsuchiya N
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, Tsukuba.
FAU - Katayama, Masao
AU  - Katayama M
AD  - Department of Internal Medicine, Nagoya Medical Center, National Hospital 
      Organization, Nagoya.
FAU - Shinohara, Satoshi
AU  - Shinohara S
AD  - Tochigi Rheumatology Clinic, Utsunomiya.
FAU - Matsui, Toshihiro
AU  - Matsui T
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, Sagamihara.
FAU - Fukui, Naoshi
AU  - Fukui N
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, Sagamihara.
FAU - Sano, Hajime
AU  - Sano H
AD  - Division of Rheumatology, Department of Internal Medicine, Hyogo College of 
      Medicine, Nishinomiya.
FAU - Migita, Kiyoshi
AU  - Migita K
AD  - Clinical Research Center, Nagasaki Medical Center, National Hospital 
      Organization, Omura.
AD  - Department of Gastroenterology and Rheumatology, Fukushima Medical University 
      School of Medicine, Fukushima, Japan.
FAU - Tohma, Shigeto
AU  - Tohma S
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, Sagamihara.
AD  - Tokyo National Hospital, National Hospital Organization, Kiyose.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Adult
MH  - *Age of Onset
MH  - Aged
MH  - Alleles
MH  - *Arthritis, Rheumatoid/diagnosis/epidemiology/genetics
MH  - Correlation of Data
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Immunologic Tests/methods
MH  - Japan/epidemiology
MH  - Male
MH  - Middle Aged
PMC - PMC6890270
COIS- Conflict of interest statement: 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 was 
      supported by research grants from Bristol-Myers Squibb Co. HF received honoraria 
      from Ajinomoto Co., Inc., Daiichi Sankyo Co., Ltd., Dainippon Sumitomo Pharma 
      Co., Ltd., Pfizer Japan Inc., and Takeda Pharmaceutical Company, Luminex Japan 
      Corporation Ltd., and Ayumi Pharmaceutical 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. 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 have no conflicts of interests 
      to disclose.
EDAT- 2019/11/27 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/11/27
CRDT- 2019/11/27 06:00
PHST- 2019/11/27 06:00 [entrez]
PHST- 2019/11/27 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/11/27 00:00 [pmc-release]
AID - 00005792-201911290-00092 [pii]
AID - MD-D-19-06185 [pii]
AID - 10.1097/MD.0000000000018218 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2019 Nov;98(48):e18218. doi: 10.1097/MD.0000000000018218.