Genetic Association Identified for RAC1 Ulcerative Colitis

Disruption of Rac1 in mice protects against dextran sulphate sodium-induced colitis

FRIDAY, Aug. 12 (HealthDay News) -- A genetic association has been identified between RAC1 and ulcerative colitis, with increased expression linked to susceptibility to colitis in humans and disruption of Rac1 in mice protecting against dextran sulphate sodium (DSS)-induced colitis, according to an experimental study published in the August issue of Gastroenterology.

Alexio M. Muise, M.D., Ph.D., from the University of Toronto, and colleagues examined the role of RAC1 in inflammatory bowel disease (IBD) using human genetic and functional studies, and animal models of colitis. A candidate gene approach was used to HapMap-Tag single-nucleotide polymorphisms (SNPs) in a discovery cohort, with findings confirmed in two additional cohorts. Peripheral blood cells of patients were used to examine RAC1 messenger RNA expression. DSS was administered to induce colitis in mice with conditional disruption of Rac1 in phagocytes.

The investigators identified a genetic correlation between RAC1 and ulcerative colitis in the discovery cohort, two additional independent replication cohorts, and in combined analysis for the SNPs rs10951982 and rs4720672. Increased expression of RAC1 was seen in patients with IBD who had the rs10951982 risk allele, compared to patients without this allele. Mice were protected against developing DSS-induced colitis by conditional disruption of Rac1 in macrophages and neutrophils.

"Human studies and knockout mice demonstrated a role for the guanosine triphosphatase RAC1 in the development of ulcerative colitis; increased expression of RAC1 was associated with susceptibility to colitis," the authors write.

Full Text (subscription or payment may be required)

Physician’s Briefing Staff

Physician’s Briefing Staff

Published on August 12, 2011

Read this Next
About UsOur ProductsCustom SolutionsHow it’s SoldOur ResultsDeliveryContact UsBlogPrivacy PolicyFAQ