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Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important inhibitor of T-lymphocyte response. Polymorphisms in the CTLA-4 gene have been reported to be associated with numerous autoimmune diseases. The aim of this study was to determine whether polymorphisms of CTLA-4 exon 1 (+49) genes are associated with susceptibility and clinicolaboratory findings of primary biliary cirrhosis (PBC) in the Japanease population. Blood samples were obtained from 45 patients (6 men and 39 women, aged 23-56 years) with PBC and 73 healthy controls (48 men and 25 women, aged 22-72 years). CTLA-4 exon 1 (+49) polymorphism was defined using a polymerase chain reaction-restriction fragment length polymorphism with Bst71I restriction enzyme. The genotype frequencies of A/A, A/G, and G/G in 45 patients with PBC were 11% (5 patients), 44% (20 patients), and 44% (20 patients), respectively. There was no significant difference between frequencies in PBC patients and healthy controls. PBC patients with G/G genotype had significantly higher serum levels of ALT, GGT, and IgM than those in patients with A/A or A/G genotype. In conclusion, CTLA-4 gene polymorphisms are not associated with susceptibility of PBC in Japan; however, G/G genotype may be associated with liver damage.

POSSIBLE ASSOCIATION OF CYTOTOXIC T LYMPHOCYTE ANTIGEN-4 GENETIC POLYMORPHISM WITH LIVER DAMAGE OF PRIMARY BILIARY CIRRHOSIS IN JAPAN