Functional evidence suggests that the A (Thr) allele increases CTLA-4 surface expression, which may modulate T-cell regulation and thus contribute to pathogenesis of autoimmune diseases such as PBC, although the possibility remains that it is a tag SNP in linkage disequilibrium with an untyped causal variant (55, 56). This evidence concerns the gene CTLA4 and primary biliary cholangitis.