Donaldson Peter T
Lecturer in Molecular Genetics, Centre for Liver Research, School of Clinical Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, United Kingdom.
Semin Liver Dis. 2002 Nov;22(4):353-64. doi: 10.1055/s-2002-35705.
Current hypotheses suggest that autoimmune hepatitis (AIH) is triggered by an environmental factor in a genetically susceptible host. Multiple genes may interact to produce a "permissive gene pool" that determines both disease risk and phenotype. Studies of type 1 AIH have focused on the major histocompatibility complex (MHC), mapping susceptibility to the DRB1 region. Three different molecular models have been proposed based on histidine at DRbeta13, lysine at DRbeta71, and valine at DRbeta86. Although the lysine-71 model has been adapted to explain data from several other studies, the DRbeta13 and DRbeta86 models are exclusive to their founder populations. It is possible that all three models apply and that the different associations reflect the "molecular footprint" of the common environmental triggers in the different study populations. Studies outside the MHC have identified the CTLA4 A+49G, G allele as a possible second risk allele. There are many neutral polymorphisms in the genome, and further studies are currently needed to identify other disease alleles in type 1 AIH.
目前的假说认为，自身免疫性肝炎（AIH）是由遗传易感性宿主中的环境因素触发的。多个基因可能相互作用，产生一个“许可基因库”，该基因库决定疾病风险和表型。1型AIH的研究主要集中在主要组织相容性复合体（MHC）上，将易感性定位到DRB1区域。基于DRβ13的组氨酸、DRβ71的赖氨酸和DRβ86的缬氨酸，提出了三种不同的分子模型。尽管赖氨酸-71模型已被用于解释其他几项研究的数据，但DRβ13和DRβ86模型仅适用于其最初的研究人群。所有三种模型都有可能适用，不同的关联反映了不同研究人群中常见环境触发因素的“分子印记”。MHC以外的研究已将CTLA4 A+49G的G等位基因确定为可能的第二个风险等位基因。基因组中存在许多中性多态性，目前需要进一步研究以确定1型AIH中的其他疾病等位基因。
