Researchers at The Hospital for Sick Children (HSC) and the University of Toronto (U of T) have identified a new human protein, OCTN3, which may be linked to Crohn’s disease. Using proteomic technologies, the protein has been identified in advance of the gene. This study demonstrates that the protein, OCTN3, exists and that its functional properties and inferred chromosomal location implicate it for involvement in Crohn’s disease. These findings provide a strategy for the identification of the corresponding gene, and may ultimately contribute to the identification of a specific group of individuals at risk for Crohn’s disease. The research is reported in the January 31 issue of the scientific journal, Biochemical and Biophysical Research Communications.
The protein, OCTN3, transports carnitine, an essential cofactor in cellular fat metabolism which generates energy for the cell and may be important for a variety of intestinal functions. Proteins from the OCTN family function primarily in the elimination of cationic drugs in the intestine, kidney, and liver. Genes encoding other related proteins in this family, namely, OCTN1 and OCTN2, map to the IBD5 locus at 5q31. Genetic variation in this 5q31 gene cluster has been previously implicated to confer susceptibility to Crohn’s disease, but no abnormalities have been found in the identified genes in this region.
The chromosomal location of the OCTN3 gene was predicted on the basis of comparison to the corresponding mouse gene family. Based upon comparisons of the mouse and human chromosomes, the researchers extrapolate the position of the human gene to reside between the OCTN1 and OCTN2 genes at human chromosome 5q31, in a region that appears to have been incompletely assembled in the human DNA sequence database.
“Our functional characterization of the OCTN3 protein indicates that it would be the most likely candidate gene of the OCTN gene family at 5q31 to confer susceptibility to Crohn’s disease. It will be vital for the Crohn’s disease research community to be aware of this gene in order to investigate its potential role in inflammatory bowel disease in those individuals with IBD5 as their contributing locus,” said Dr. Ingrid Tein, the study’s principal investigator, an HSC neurologist and scientist, and an associate professor at U of T.
Inflammatory bowel disease occurs in 200 to 300 per 100,000 people. At The Hospital for Sick Children there are currently 300 patients being treated for Crohn’s disease. Many of the children seen at the clinic have familial Crohn’s disease.
The other members of the research team are: Dr. Anne-Marie Lamhonwah, Dr. Stephen Scherer, and Jennifer Skaug, all from The Hospital for Sick Children.
This research was supported by the Heart and Stroke Foundation of Ontario and The Hospital for Sick Children Foundation.
Jennifer ten Westeneind is Communications is Coordinator at The Hospital for Sick Children.