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Abstract

Background: Primary biliary cirrhosis (PBC) is a complex disease with genetic and environmental influences. The disease is more prevalent in families with PBC and candidate gene case–control studies have linked PBC with DRB1*08 human leucocyte antigen class II alleles.

Aims: The goal of this study was to characterize a MER115 intergenic region on chromosome 4 as a putative genetic variant associated with PBC.

Methods/Results: This region was incidentally identified during investigations to discover candidate microbial agents using representational difference analysis (RDA) with liver samples from patients with PBC and primary sclerosing cholangitis (PSC). blast search analysis of all the RDA products from the PBC liver revealed genomic sequences, whereas Escherichia coli, mycoplasma and hepatitis B virus DNA were found in the PSC liver. We identified one of the PBC RDA products as an ancestral repeat, referred to as MER115. Southern blot analysis with the PBC product uncovered a restriction fragment length polymorphism in PBC patients' liver. Southern blot hybridization signal showed increased signal intensity in PBC vs. control patients' DNA (P<0.005) and slot blot hybridization studies confirmed a copy number variation of the MER115 in hepatic DNA of PBC vs. control patients (P=0.02).

Conclusions: Further comparative genetic studies will be required to determine the extent of genomic duplication associated with MER115 and provide data on the possible copy number variants of genes close to this intergenic region in patients with PBC.