Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease

摘要: Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of population, remain obscure. Here we identify polymorphisms cytotoxic T lymphocyte antigen 4 gene (CTLA4)—which encodes a vital negative regulatory molecule immune system—as candidates for primary determinants risk Graves' disease, hypothyroidism type 1 diabetes. In humans, disease susceptibility was mapped to non-coding 6.1?kb 3′ region CTLA4, allelic variation which correlated with lower messenger RNA levels soluble alternative splice form CTLA4. mouse model diabetes, also associated CTLA-4 splicing reduced production encoding lacking CD80/CD86 ligand-binding domain. Genetic mapping variants conferring small can pathways disorders, exemplified by our discovery inherited, quantitative alterations CTLA4 contributing tissue destruction.