Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis

Genetic susceptibility to type 1 autoimmune hepatitis is indicated by a pre ponderance of female subjects and strong associations with human Leukocyte antigens (HLA) DRB1*0301 and DRB1*0401. The gene encoding cytotoxic T-lymph ocyte antigen-4 (CTLA-4) on chromosome 2q33 may also influence autoimmunity . To determine the frequency and significance of the exon 1 adenine (A)-gua nine (G) base-exchange polymorphism for CTLA-4 in patients with type 1 auto immune hepatitis, 155 northern European Caucasoid patients and 102 ethnical ly-matched control subjects were tested by polymerase chain reaction. The g enotype distribution was significantly different in patients compared to co ntrols (AA = 50/155 patients vs. 51/102 controls; AG = 84/155 patients vs. 38/102 controls; GG 21/155 patients vs. 13/102 controls, chi(2) = 8.94, P = .011), This difference was caused by a significant over-representation of the G allele in patients compared to controls (105/155 patients vs. 51/102 controls, chi(2) = 8.34, P = .004, odds ratio = 2.12). The GG genotype was associated with a significantly higher mean serum aspartate transaminase le vel (P = .03), greater frequency of antibodies to thyroid microsomal antige ns (P = .004) and was found more commonly in patients with HLA DRB1*0301 (P = .02), Treatment outcomes, however, were not affected by the genotype, Th e CTLA-4 G allele is more common in patients with type 1 autoimmune hepatit is and may represent a second susceptibility allele, Furthermore, there may be synergy between the HLA-DRB1*0301 and the GG genotype in terms of disea se risk.