Role of genetics in immunopathogenesis

摘要

For most common diseases, including heart disease, diabetes, hypertension, cancer, and both autoimmune and viral liver disease, genes are likely to determine an individual's 'disease risk'1"3. However, the diseases autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSQ are not single-gene Mendelian diseases, they are genetically 'complex'. They are for the most part multifactorial, polygenic disorders, where possession of a specific genetic variant (mutation or polymorphism) at a locus (an allele) simply increases or reduces the risk of disease (a trait) developing2. Moreover, possession of a disease-promoting allele (or disease-causing mutation, DCM) does not by itself lead to disease (incomplete penetrance); other disease-promoting alleles and/or encounter with specific environmental factors may be necessary for disease expression. In addition, not all of the DCM identified in complex disease are involved in disease initiation; many polymorphisms and mutations act to determine the clinical phenotype of a disease, for example: severity, progression and response to treatment.