title: Identification of OCTN2 variants and their association with phenotypes of Crohn's disease in a Korean population.
abstract: Crohn's disease (CD) is a chronic inflammatory bowel disease and a genetic variant in the OCTN2, g.-207G > C is significantly associated with CD susceptibility. This study was aimed to identify novel OCTN2 functional promoter variants and their roles in transcriptional regulation using various in vitro assays. In addition, we investigated the association between OCTN2 genotypes and CD through genetic analysis using DNA samples from 193 patients with CD and 281 healthy controls. Among the three major promoter haplotypes of OCTN2 identified, one haplotype, H3, showed a significant decrease in promoter activity: two polymorphisms in H3 were associated with a significant reduction in promoter activity. In particular, we found that the reduced transcriptional activity of those two polymorphisms results from a reduction in the binding affinity of the activators, NF-E2 and YY1, to the OCTN2 promoter. The functional haplotype of the OCTN2 promoter was associated with clinical course of CD such as the disease behavior and need for surgery. However, genetic variants or haplotypes of OCTN2 did not affect the susceptibility to CD. Our results suggest that a common promoter haplotype of OCTN2 regulates the transcriptional rate of OCTN2 and influences the clinical course of CD.
authors.affiliation: Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, 07985, Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, 03722, Korea.|Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, Korea.
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Jung
authors.affiliation: Clinical Trial Center, Ewha Womans University Medical Center, Seoul, 07985, Korea.
authors.forename: Kyoung Ae
authors.initials: KA
authors.lastname: Kong
authors.affiliation: Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, 07985, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
authors.affiliation: Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, 07985, Korea.
authors.forename: Ji Ha
authors.initials: JH
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D002648:Child; D003424:Crohn Disease / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D050983:NF-E2 Transcription Factor / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D056910:Republic of Korea; D000074058:Solute Carrier Family 22 Member 5; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D050986:YY1 Transcription Factor; D055815:Young Adult
chemical_list: D050983:NF-E2 Transcription Factor; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human