Crohns disease (CD) is a chronic inflammatory bowel disease with multifactorial causes including environmental and genetic factors. Several studies have demonstrated that the organic cation/carnitine transporter 1 (OCTN1) nonsynonymous variant L503F is associated with susceptibility to CD. However, it was reported that L503F is absent in Asian populations. Previously, we identified and functionally characterized genetic variants of the OCTN1 promoter region in Koreans. In that study, four variants demonstrated significant changes in promoter activity. In the present study, we determined whether four functional variants of the OCTN1 promoter play a role in the susceptibility to or clinical course of CD in Koreans. To examine it, the frequencies of the four variants of the OCTN1 promoter were determined by genotyping using DNA samples from 194 patients with CD and 287 healthy controls. Then, associations between genetic variants and the susceptibility to CD or clinical course of CD were evaluated. We found that susceptibility to CD was not associated with OCTN1 functional promoter variants or haplotypes showing altered promoter activities in in vitro assays. However, OCTN1 functional promoter haplotypes showing decreased promoter activities were significantly associated with a penetrating behavior in CD patients (HR=2.428, p=0.009). Our results suggest that the OCTN1 functional promoter haplotypes can influence the CD phenotype, although these might not be associated with susceptibility to this disease.
Bibliographical noteFunding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning [2010-0027945 and 2013R1A2A2A01067123], and grants from the National Project for Personalized Genomic Medicine [A111218-PG03] and the Korean Health Technology R and D Project [A120176], Ministry for Health and Welfare, Korea.
© Copyright Korean J Physiol Pharmacol.
All Science Journal Classification (ASJC) codes