Genetic polymorphisms of transforming growth factor beta-1 promoter and primary biliary cirrhosis in Japanese patients.

As suggested by concordance rates in twins, genetic factors are critical to the susceptibility and progression of primary biliary cirrhosis (PBC). Among cytokines, transforming growth factor beta-1 (TGF-beta1) plays an important role in autoimmunity and liver fibrosis and a TGF-beta1 receptor knockout mouse has been recently proposed as a model for PBC. The promoter region of the TGF-beta1 gene has two single nucleotide polymorphisms (SNPs) at positions -800 and -509, which influence serum concentrations of latent and active TGF-beta1. We studied genomic DNA from 65 Japanese patients with PBC and 71 matched healthy controls for the association of TGF-beta1 SNPs analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with susceptibility and disease progression of PBC. The -800 G to A SNP was not found in the Japanese population and no significant difference in the distribution of TGF-beta1 promoter gene -509 SNP was found between PBC cases and controls. Further, TGF-beta1 genotypes failed to correlate with clinical parameters, including histological stage and prognostic score. In conclusion, the TGF-beta1 promoter gene SNPs are not associated with disease susceptibility or progression in Japanese patients with PBC.