Genetics in autoimmune hepatitis

PT Donaldson - Seminars in liver disease, 2002 - thieme-connect.com
PT Donaldson
Seminars in liver disease, 2002thieme-connect.com
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 DRβ13, lysine at DRβ71, and valine at DRβ86. Although the lysine-71 …
Abstract
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 DRβ13, lysine at DRβ71, and valine at DRβ86. Although the lysine-71 model has been adapted to explain data from several other studies, the DRβ13 and DRβ86 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.
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