Genetic associations discovered for primary sclerosing cholangitis

This month's Gastroenterology reports on a genome-wide association analysis in primary sclerosing cholangitis.

Dr Tom Karlsen and colleagues from Norway characterized the genetic susceptibility to primary sclerosing cholangitis by means of a genome-wide association analysis of single nucleotide polymorphism markers.

The team evaluated a total of 443,816 single nucleotide polymorphisms on the Affymetrix single nucleotide polymorphism Array 5.0 in 285 Norwegian primary sclerosing cholangitis patients, and 298 healthy controls.

Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia, The Netherlands, and Germany.

Macrophage-stimulating 1 is onr of the likely disease genes

Gastroenterology

Outside the HLA complex, rs9524260 at chromosome 13q31 showed significant associations in 3 of 4 study panels.

Lentiviral silencing of glypican 6, encoded at this locus, led to the up-regulation of proinflammatory markers in a cholangiocyte cell line.

Of 15 established ulcerative colitis susceptibility loci, significant replication was obtained at chromosomes 2q35 and 3p21.

There was circumstantial evidence supporting the G-protein–coupled bile acid receptor 1 and macrophage-stimulating 1, respectively, as the likely disease genes.

Dr Karlsen's team concluded. “Strong HLA associations and a subset of genes involved in bile homeostasis and other inflammatory conditions constitute key components of the genetic architecture of primary sclerosing cholangitis.”