Jung Eun Suk, Park Hyo Jin, Kong Kyoung Ae, Choi Ji Ha, Cheon Jae Hee
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.
Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul 07985, Korea.
Korean J Physiol Pharmacol. 2017 Jan;21(1):11-17. doi: 10.4196/kjpp.2017.21.1.11. Epub 2016 Dec 21.
Crohn's 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 () non-synonymous 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 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 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 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 functional promoter variants or haplotypes showing altered promoter activities in assays. However, 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 functional promoter haplotypes can influence the CD phenotype, although these might not be associated with susceptibility to this disease.
克罗恩病（CD）是一种慢性炎症性肠病，其病因多因素，包括环境和遗传因素。多项研究表明，有机阳离子/肉碱转运体1（）非同义变体L503F与CD易感性相关。然而，有报道称亚洲人群中不存在L503F。此前，我们鉴定并在功能上表征了韩国人中该启动子区域的遗传变异。在该研究中，四个变体在启动子活性方面表现出显著变化。在本研究中，我们确定该启动子的四个功能变体是否在韩国人CD的易感性或临床病程中起作用。为了对此进行研究，使用194例CD患者和287例健康对照的DNA样本进行基因分型，确定该启动子四个变体的频率。然后，评估遗传变异与CD易感性或CD临床病程之间的关联。我们发现，CD易感性与该功能启动子变体或在检测中显示启动子活性改变的单倍型无关。然而，显示启动子活性降低的该功能启动子单倍型与CD患者的穿透性行为显著相关（风险比=2.428，p=0.009）。我们的结果表明，该功能启动子单倍型可影响CD表型，尽管这些可能与该病的易感性无关。
