Association of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with type 1 autoimmune hepatitis in Japanese.

AIM: Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver. Although the HLA DR4 allele is associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains undefined. The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed by T-cells that acts largely as a negative regulator of T-cell responses, and polymorphisms of CTLA4 have been reported to be associated with susceptibility to various autoimmune diseases. Therefore, we sought to clarify whether CTLA4 single-nucleotide polymorphisms are associated with disease susceptibility in Japanese patients with type 1 AIH.

METHODS

We genotyped 76 patients with AIH and 100 ethically matched controls for allelic determinants using TaqMan genotyping assays at four polymorphism sites: -1722 and -318 in the promoter; +49 in exon 1 and +6230 in the 3' untranslated region.

RESULTS

We observed no difference in the distribution of the alleles, genotypes, or haplotypes between patients and controls. Compared with -1722 C/C patients, -1722 T/T patients were younger (56 vs. 63 years; P = 0.01) and had significantly lower serum levels of aspartate aminotransferase (313 vs. 763 IU/L; P = 0.031) and bilirubin (1.1 vs. 8.6 mg/dL; P = 0.027). Analysis of allelic frequencies revealed no significant difference between patients with and without the HLA DR4 allele.

CONCLUSION

These data suggest that the CTLA4 polymorphism is not associated with susceptibility to type 1 AIH in the Japanese population.