Epitope shared by functional variant of organic cation/carnitine transporter, OCTN1, Campylobacter jejuni and Mycobacterium paratuberculosis may underlie susceptibility to Crohn's disease at 5q31.

摘要: Campylobacter jejuni and Mycobacterium paratuberculosis have been implicated in the pathogenesis of Crohn's disease. The presence bacterial metabolites colonic lumen causing a specific breakdown fatty acid oxidation epithelial cells has suggested as an initiating event inflammatory bowel disease (IBD). l-Carnitine is small highly polar zwitterion that plays essential role ATP generation intestinal bioenergetic metabolism. organic cation/carnitine transporters, OCTN1 OCTN2, function primarily transport l-carnitine elimination cationic drugs intestine. High-resolution linkage disequilibrium mapping identified region about 250kb size at 5q31 (IBD5) encompassing -2 genes, to confer susceptibility Recently, two variants OCTN2 genes shown form haplotype which associated with Crohn's. We show are strongly expressed target areas for IBD such ileum colon. Further, we now nine amino epitope shared by this functional variant (Leu503Phe) (which decreases efficiency carnitine transport), C. (9 aa) M. (6 aa). prevalence (Phe503:Leu503) 3-fold lower unaffected individuals Jewish origin (1:3.44) compared non-Jewish (1:1). hypothesize antibody raised during or enterocolitis would cross-react cell OCTN1, already less efficient transporter, leading impairment mitochondrial beta-oxidation may then serve IBD. This respond high-dose therapy.