PMID- 33509297
OWN - NLM
STAT- MEDLINE
DCOM- 20220204
LR  - 20220204
IS  - 1479-7364 (Electronic)
IS  - 1473-9542 (Print)
IS  - 1473-9542 (Linking)
VI  - 15
IP  - 1
DP  - 2021 Jan 28
TI  - Genetic risk factors for autoimmune hepatitis: implications for phenotypic 
      heterogeneity and biomarkers for drug response.
PG  - 6
LID - 10.1186/s40246-020-00301-4 [doi]
LID - 6
AB  - Autoimmune hepatitis (AIH) is a rare chronic progressive liver disease with 
      autoimmune features. It mainly affects middle-aged women. AIH is occasionally 
      complicated with liver cirrhosis that worsens the prognosis. Genetic and 
      environmental factors are involved in the pathogenesis of AIH. Genetic studies of 
      other diseases have been revealing of pathogenesis and drug efficacy. In this 
      review, we summarize the genetic risk factors for AIH, including human leukocyte 
      antigen (HLA) and non-HLA genes. A genome-wide association study (GWAS) on 
      European AIH revealed the strongest associations to be with single nucleotide 
      variants (SNVs) in HLA. Predisposing alleles for AIH were DRB1*03:01 and 
      DRB1*04:01 in Europeans; DRB1*04:04, DRB1*04:05, and DRB1*13:01 in Latin 
      Americans; and DRB1*04:01 and DRB1*04:05 in Japanese. Other risk SNVs in non-HLA 
      genes for AIH were found by a candidate gene approach, but several SNVs were 
      confirmed in replication studies. Some genetic factors of AIH overlapped with 
      those of other autoimmune diseases. Larger-scale GWASs of other ethnic groups are 
      required. The results of genetic studies might provide an explanation for the 
      phenotypic heterogeneity of AIH and biomarkers for drug responses.
FAU - Higuchi, Takashi
AU  - Higuchi T
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
AD  - Department of Nephrology, Ushiku Aiwa General Hospital, 896 Shishiko-cho, Ushiku, 
      300-1296, Japan.
AD  - Department of Rheumatology, National Hospital Organization Tokyo National 
      Hospital, 3-1-1 Takeoka, Kiyose, 204-8585, Japan.
FAU - Oka, Shomi
AU  - Oka S
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
AD  - Department of Rheumatology, National Hospital Organization Tokyo National 
      Hospital, 3-1-1 Takeoka, Kiyose, 204-8585, Japan.
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, 
      252-0392, Japan.
FAU - Furukawa, Hiroshi
AU  - Furukawa H
AUID- ORCID: 0000-0003-1353-8056
AD  - Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of 
      Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan. furukawa-tky@umin.org.
AD  - Department of Rheumatology, National Hospital Organization Tokyo National 
      Hospital, 3-1-1 Takeoka, Kiyose, 204-8585, Japan. furukawa-tky@umin.org.
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, 
      252-0392, Japan. furukawa-tky@umin.org.
FAU - Tohma, Shigeto
AU  - Tohma S
AD  - Department of Rheumatology, National Hospital Organization Tokyo National 
      Hospital, 3-1-1 Takeoka, Kiyose, 204-8585, Japan.
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, 
      252-0392, Japan.
FAU - Yatsuhashi, Hiroshi
AU  - Yatsuhashi H
AD  - Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 
      2-1001-1 Kubara, Omura, 856-8562, Japan.
FAU - Migita, Kiyoshi
AU  - Migita K
AD  - Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 
      2-1001-1 Kubara, Omura, 856-8562, Japan.
AD  - Department of Rheumatology, Fukushima Medical University School of Medicine, 1 
      Hikarigaoka, Fukushima, 960-1295, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210128
PL  - England
TA  - Hum Genomics
JT  - Human genomics
JID - 101202210
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Biomarkers, Pharmacological/*blood
MH  - Genetic Heterogeneity
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA Antigens/*genetics
MH  - Hepatitis, Autoimmune/drug therapy/*genetics/pathology
MH  - Humans
MH  - Phenotype
MH  - Risk Factors
PMC - PMC7841991
OTO - NOTNLM
OT  - Autoimmune hepatitis
OT  - Genetic risk factor
OT  - HLA
OT  - Liver cirrhosis
OT  - Single nucleotide variant
COIS- HY was supported by research grants from AbbVie GK. The other authors declare no 
      financial or commercial conflicts of interest.
EDAT- 2021/01/30 06:00
MHDA- 2022/02/05 06:00
PMCR- 2021/01/28
CRDT- 2021/01/29 05:39
PHST- 2020/10/21 00:00 [received]
PHST- 2020/12/15 00:00 [accepted]
PHST- 2021/01/29 05:39 [entrez]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2022/02/05 06:00 [medline]
PHST- 2021/01/28 00:00 [pmc-release]
AID - 10.1186/s40246-020-00301-4 [pii]
AID - 301 [pii]
AID - 10.1186/s40246-020-00301-4 [doi]
PST - epublish
SO  - Hum Genomics. 2021 Jan 28;15(1):6. doi: 10.1186/s40246-020-00301-4.