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Review
. 2021 Jan 28;15(1):6.
doi: 10.1186/s40246-020-00301-4.

Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response

Takashi Higuchi  1   2   3 , Shomi Oka  1   3   4 , Hiroshi Furukawa  5   6   7 , Shigeto Tohma  3   4 , Hiroshi Yatsuhashi  8 , Kiyoshi Migita  8   9
Affiliations
Review

Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response

Takashi Higuchi et al. Hum Genomics. .

Abstract

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.

Keywords: Autoimmune hepatitis; Genetic risk factor; HLA; Liver cirrhosis; Single nucleotide variant.

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Conflict of interest statement

HY was supported by research grants from AbbVie GK. The other authors declare no financial or commercial conflicts of interest.

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