Jie Tang1, Cheng Zhou, Zhi-Jun Zhang, Shu-Sen Zheng. 1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Abstract
BACKGROUND: Autoimmune hepatitis is a chronic, generally progressive inflammatory disorder of the liver, of which the cause is unclear. It was demonstrated that genetic factors are involved in its pathogenesis. Previous studies showed that human leukocyte antigen in the major histocompatibility complex (MHC) is associated with susceptibility to autoimmune hepatitis. Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders. This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis, polymorphism, CTLA-4, Fas, TNF-alpha, TGF-beta1, TBX21 and VDR up to May 2011. Additional papers were identified by a manual search of the references from key articles. RESULTS: According to the case-control studies on genetic polymorphisms, at least six genes (CTLA-4, Fas, TNF-alpha, TGF-beta1, TBX21 and VDR) are involved in autoimmune hepatitis besides HLA. So far, there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial. CONCLUSION: Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms, but also provide new targets for therapy in the future.
BACKGROUND:Autoimmune hepatitis is a chronic, generally progressive inflammatory disorder of the liver, of which the cause is unclear. It was demonstrated that genetic factors are involved in its pathogenesis. Previous studies showed that human leukocyte antigen in the major histocompatibility complex (MHC) is associated with susceptibility to autoimmune hepatitis. Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders. This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis, polymorphism, CTLA-4, Fas, TNF-alpha, TGF-beta1, TBX21 and VDR up to May 2011. Additional papers were identified by a manual search of the references from key articles. RESULTS: According to the case-control studies on genetic polymorphisms, at least six genes (CTLA-4, Fas, TNF-alpha, TGF-beta1, TBX21 and VDR) are involved in autoimmune hepatitis besides HLA. So far, there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial. CONCLUSION: Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms, but also provide new targets for therapy in the future.