Dong-Hoon Yang1, Suk-Kyun Yang2, Kyuyoung Song3, Myunghee Hong4, Sang Hyoung Park1, Ho-Su Lee1, Ji-Beom Kim1, Hyo Jeong Lee1, Soo-Kyung Park1, Kee Wook Jung1, Kyung-Jo Kim1, Byong Duk Ye1, Jeong-Sik Byeon1, Seung-Jae Myung1, Jin-Ho Kim1, Ui Sup Shin5, Chang Sik Yu6, Inchul Lee7. 1. Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. 2. Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: sky@amc.seoul.kr. 3. Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: kysong@amc.seoul.kr. 4. Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea. 5. Department of Surgery, Korea Institute of Radiological and Medical Sciences, Korea Cancer Center Hospital, Seoul, South Korea. 6. Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. 7. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Abstract
BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory bowel disease involving the whole gastrointestinal tract. TNFSF15 has been proved as a susceptibility gene for CD, but there are few reports about the association between TNFSF15 single nucleotide polymorphisms (SNPs) and the clinical course of CD. AIM: To investigate the association between TNFSF15 genotypes and the clinical course of CD in Koreans. METHODS: A total of 906 CD patients having TNFSF15 genotype data and clinical information were recruited from CD registry database of a tertiary referral center. The association between five TNFSF15 SNPs (rs4574921, rs3810936, rs6478108, rs6478109, and rs7848647) and various clinical parameters including stricture, non-perianal penetrating complications, bowel resection, and reoperation was investigated. RESULTS: Among the five SNPs, rs6478108 CC genotype was associated with the development of stricture and non-perianal penetrating complications during follow-up (HR for stricture=1.706, 95% confidence interval 1.178-2.471, P=0.005; HR for non-perianal penetrating complications=1.667, 95% confidence interval 1.127-2.466, P=0.010), and rs4574921 CC genotype was associated with the development of perianal fistula (HR=2.386, 95% confidence interval 1.204-4.727, P=0.013) by multivariate analysis. However, there was no significant association of cumulative operation and reoperation rate with 5 SNPs of TNFSF15. CONCLUSION: In Korean patients with CD, non-risk allele homozygotes of TNFSF15 SNPs rs6478108 and rs4574921 are independent genetic predictive factors for the development of strictures/non-perianal penetrating complications and perianal fistula, respectively.
BACKGROUND:Crohn's disease (CD) is a chronic idiopathic inflammatory bowel disease involving the whole gastrointestinal tract. TNFSF15 has been proved as a susceptibility gene for CD, but there are few reports about the association between TNFSF15 single nucleotide polymorphisms (SNPs) and the clinical course of CD. AIM: To investigate the association between TNFSF15 genotypes and the clinical course of CD in Koreans. METHODS: A total of 906 CDpatients having TNFSF15 genotype data and clinical information were recruited from CD registry database of a tertiary referral center. The association between five TNFSF15 SNPs (rs4574921, rs3810936, rs6478108, rs6478109, and rs7848647) and various clinical parameters including stricture, non-perianal penetrating complications, bowel resection, and reoperation was investigated. RESULTS: Among the five SNPs, rs6478108 CC genotype was associated with the development of stricture and non-perianal penetrating complications during follow-up (HR for stricture=1.706, 95% confidence interval 1.178-2.471, P=0.005; HR for non-perianal penetrating complications=1.667, 95% confidence interval 1.127-2.466, P=0.010), and rs4574921 CC genotype was associated with the development of perianal fistula (HR=2.386, 95% confidence interval 1.204-4.727, P=0.013) by multivariate analysis. However, there was no significant association of cumulative operation and reoperation rate with 5 SNPs of TNFSF15. CONCLUSION: In Korean patients with CD, non-risk allele homozygotes of TNFSF15 SNPs rs6478108 and rs4574921 are independent genetic predictive factors for the development of strictures/non-perianal penetrating complications and perianal fistula, respectively.
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