Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response.
Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response.
复制标题
DOI：
10.1186/s40246-020-00301-4
复制
发表时间：
2021-01-28
期刊：
影响因子：
4.5
通讯作者：
Migita K
中科院分区：
文献类型：
--
作者：
Higuchi T;Oka S;Furukawa H;Tohma S;Yatsuhashi H;Migita K
自身免疫性肝炎（AIH）是一种罕见的慢性进行性肝病，具有自身免疫性特征。它主要影响中年妇女。AIH偶尔合并肝硬化，影响预后。遗传和环境因素参与了AIH的发病机制。对其他疾病的遗传学研究也揭示了其发病机制和药物疗效。本文就AIH的遗传危险因素，包括人类白细胞抗原（HLA）基因和非HLA基因进行综述。一项关于欧洲AIH的全基因组关联研究（GWAS）揭示了与HLA中单核苷酸变异（SNV）的最强关联。AIH的易感等位基因在欧洲人中为DRB 1 *03：01和DRB 1 *04：01;在拉丁美洲人中为DRB 1 * 04：04、DRB 1 *04：05和DRB 1 *13：01;在日本人中为DRB 1 *04：01和DRB 1 *04：05。通过候选基因方法发现了AIH非HLA基因中的其他风险SNV，但在复制研究中证实了几个SNV。AIH的某些遗传因素与其他自身免疫性疾病的遗传因素有重叠。需要对其他族裔群体进行更大规模的全球水资源评估。遗传学研究的结果可能为AIH的表型异质性和药物反应的生物标志物提供解释。在线版本包含补充材料，可通过10.1186/s40246-020-00301-4获得。
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. The online version contains supplementary material available at 10.1186/s40246-020-00301-4.
登录
查看更多内容
影响因子：
13.5
作者：
Agarwal, K;Czaja, AJ;Donaldson, PT
通讯作者：
Donaldson, PT
影响因子：
9.8
作者：
Bittencourt, PL;Palácios, SA;Goldberg, AC
通讯作者：
Goldberg, AC
影响因子：
2.7
作者：
Baharlou, Rasoul;Faghihi-Kashani, Amirhossein;Tajik, Nader
通讯作者：
Tajik, Nader
影响因子：
64.8
作者：
Dong, C;Juedes, AE;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
13.5
作者：
Cookson, S;Constantini, PK;Donaldson, PT
通讯作者：
Donaldson, PT