PMID- 24956105
OWN - NLM
STAT- MEDLINE
DCOM- 20151105
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - Human leukocyte antigen class II haplotypes affect clinical characteristics and 
      progression of type 1 autoimmune hepatitis in Japan.
PG  - e100565
LID - 10.1371/journal.pone.0100565 [doi]
LID - e100565
AB  - Although we earlier demonstrated that the human leukocyte antigen (HLA) 
      DRB1*04:05 allele was associated with susceptibility to autoimmune hepatitis 
      (AIH) in Japan, the precise relationship of HLA haplotype and the role of amino 
      acid alignment with disease susceptibility and progression has not been fully 
      clarified. We reinvestigated HLA class I A, B, and C and HLA class II DRB1, DQB1, 
      and DPB1 alleles and haplotypes in a larger new cohort of 156 Japanese patients 
      with type 1 AIH and compared them with the published data of 210 healthy 
      subjects. The DRB1*04:05-DQB1*04:01 haplotype was significantly associated with 
      AIH susceptibility (30% vs. 11%, P = 1.2x10(-10); odds ratio [OR]  = 3.51) and 
      correlated with elevated serum IgG (3042 vs. 2606 mg/dL, P = 0.041) and 
      anti-smooth muscle antigen positivity (77% vs. 34%, P = 0.000006). No 
      associations with HLA-DPB1 alleles were found. The HLA A*24:02 and C*01:02 
      alleles were associated with disease susceptibility (corrected P = 0.0053 and 
      0.036, respectively), but this likely constituents of a long ranged haplotype 
      including DRB1*04:05-DQB1*04:01 haplotype. Conversely, the DRB1*15:01-DQB1*06:02 
      haplotype was associated with protection from both disease onset (5% vs. 13%, 
      P = 0.00057; OR = 0.38) and the development of hepatocellular carcinoma (25% vs. 
      5%, P = 0.017; OR = 6.81). The frequency of the DRB1*08:03-DQB1*06:01 haplotype 
      was significantly higher in patients who developed hepatic failure (22% vs. 6%, 
      P = 0.034; OR = 4.38). In conclusion, this study established the role of HLA 
      haplotypes in determining AIH susceptibility and progression in the Japanese 
      population. Additional sequencing of the entire HLA region is required to more 
      precisely identify the genetic components of AIH.
FAU - Umemura, Takeji
AU  - Umemura T
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Katsuyama, Yoshihiko
AU  - Katsuyama Y
AD  - Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
FAU - Yoshizawa, Kaname
AU  - Yoshizawa K
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan; Department of Gastroenterology, 
      NHO Ueda Medical Center, Ueda, Japan.
FAU - Kimura, Takefumi
AU  - Kimura T
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Joshita, Satoru
AU  - Joshita S
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Komatsu, Michiharu
AU  - Komatsu M
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Matsumoto, Akihiro
AU  - Matsumoto A
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Tanaka, Eiji
AU  - Tanaka E
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Ota, Masao
AU  - Ota M
AD  - Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140623
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Aged
MH  - Disease Progression
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Predisposition to Disease
MH  - Haplotypes/*genetics
MH  - Hepatitis, Autoimmune/epidemiology/*genetics/*immunology
MH  - Histocompatibility Antigens Class I/chemistry/*genetics
MH  - Histocompatibility Antigens Class II/chemistry/*genetics
MH  - Humans
MH  - Japan/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Protein Conformation
PMC - PMC4067340
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/24 06:00
MHDA- 2015/11/06 06:00
PMCR- 2014/06/23
CRDT- 2014/06/24 06:00
PHST- 2014/03/20 00:00 [received]
PHST- 2014/05/25 00:00 [accepted]
PHST- 2014/06/24 06:00 [entrez]
PHST- 2014/06/24 06:00 [pubmed]
PHST- 2015/11/06 06:00 [medline]
PHST- 2014/06/23 00:00 [pmc-release]
AID - PONE-D-14-12567 [pii]
AID - 10.1371/journal.pone.0100565 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 23;9(6):e100565. doi: 10.1371/journal.pone.0100565. 
      eCollection 2014.