Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Institute for Life Sciences, Seoul, Korea.
J Gastroenterol Hepatol. 2018 Apr;33(4):887-893. doi: 10.1111/jgh.14031. Epub 2018 Feb 5.
CDKN2A/CDKN2B locus on 9p21 is reported to be associated with various diseases, including cancer and cardiovascular and inflammatory diseases. Significant downregulation of CDKN2B-AS1 in inflamed colon tissue of inflammatory bowel disease (IBD) cases was reported in Europeans. This study aimed to confirm the suggestive association of CDKN2A/CDKN2B with IBD identified in our recent genome-wide association study (GWAS).
We examined the association of CDKN2A/CDKN2B locus with IBD in an additional sample of 574 IBD cases and 542 controls, totaling 4068 cases and 8074 controls. In silico study was performed at various levels for functional annotation of the causal variant. Co-localization of the GWAS association signals and the corresponding expression quantitative trait loci in IBD-related tissues was evaluated using eCAVIAR.
An expanded GWAS showed genome-wide significant association of rs3731257 at 9p21 with IBD (odds ratio = 1.17, 95% confidence interval = 1.12-1.22, P = 5.68 × 10 ) and Crohn's disease (odds ratio = 1.22, 95% confidence interval = 1.15-1.28, P = 8.85 × 10 ) in the Korean population. Co-localization study suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated with the locus in the small intestine.
rs3731257 in CDKN2A/CDKN2B is an IBD-susceptible locus in Koreans, with a suggestive role for small intestine-specific gene regulation. Our findings suggested that alterations of the CDKN2A/CDKN2B locus could affect the pathophysiology of IBD.
9p21 上的 CDKN2A/CDKN2B 基因座与多种疾病相关，包括癌症、心血管疾病和炎症性疾病。有报道称，在欧洲的炎症性肠病（IBD）病例的炎症结肠组织中，CDKN2B-AS1 的表达显著下调。本研究旨在验证我们最近的全基因组关联研究（GWAS）中发现的 CDKN2A/CDKN2B 与 IBD 之间的关联。
我们在另外 574 例 IBD 病例和 542 例对照中检查了 CDKN2A/CDKN2B 基因座与 IBD 的关联，总共有 4068 例病例和 8074 例对照。通过在不同水平上进行全基因组关联信号的功能注释的研究，评估了在 IBD 相关组织中 GWAS 关联信号和相应的表达数量性状基因座的共定位。
一项扩展的 GWAS 显示，9p21 上的 rs3731257 与 IBD（比值比=1.17，95%置信区间=1.12-1.22，P=5.68×10 ）和克罗恩病（比值比=1.22，95%置信区间=1.15-1.28，P=8.85×10 ）在韩国人群中具有全基因组显著关联。共定位研究表明，CDKN2B-AS1 和 CDKN2A 可能在小肠中与该基因座具有功能相关性。
CDKN2A/CDKN2B 上的 rs3731257 是韩国人 IBD 的易感基因座，提示小肠特异性基因调控的作用。我们的研究结果表明，CDKN2A/CDKN2B 基因座的改变可能会影响 IBD 的病理生理学。
