A2BP1 as a novel susceptible gene for primary biliary cirrhosis in Japanese patients

概要

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Primary biliary cirrhosis (PBC) is a complex autoimmune liver disease with an etiology that remains to be conclusively elucidated. As such, we screened the human genome for genes that might influence PBC susceptibility or resistance using 400 microsatellite markers. A strong candidate gene indicated by susceptibility microsatellite markers was further evaluated by association analysis using single nucleotide polymorphisms (SNPs). A total of 126 patients with PBC and 95 healthy Japanese controls were enrolled. Four candidate susceptible regions and seven candidate protective regions were statistically associated with PBC. Because the D16S423 marker on chromosome 16p showed the strongest evidence of linkage, the protein-coding gene ataxin 2-binding protein 1 (A2BP1) lying 27 kb on the centromeric side of D16S423 was targeted as a candidate susceptible gene. Seven SNPs (rs17139207, rs12926282, rs17139244, rs6500742, rs4146812, rs4124065, and rs889699) in the A2BP1 gene were genotyped in patients and controls. The rs17139244 SNP was found to be weakly associated with PBC in an additive model. The genotype frequency of the major C allele at rs6500742 was significantly associated with PBC, compared with healthy controls. This study showed a total of 11 candidate PBC susceptibility or resistance regions. In particular, the A2BP1 gene might play a pivotal role for susceptibility to PBC.