TNFSF15 is an independent predictor for the development of Crohn's disease-related complications in Koreans.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Dong-Hoon
DH
Yang
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: sky@amc.seoul.kr.
Suk-Kyun
SK
Yang
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: kysong@amc.seoul.kr.
Kyuyoung
K
Song
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea.
Myunghee
M
Hong
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Sang Hyoung
SH
Park
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Ho-Su
HS
Lee
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Ji-Beom
JB
Kim
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Hyo Jeong
HJ
Lee
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Soo-Kyung
SK
Park
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Kee Wook
KW
Jung
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Kyung-Jo
KJ
Kim
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Byong Duk
BD
Ye
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Jeong-Sik
JS
Byeon
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Seung-Jae
SJ
Myung
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Jin-Ho
JH
Kim
Department of Surgery, Korea Institute of Radiological and Medical Sciences, Korea Cancer Center Hospital, Seoul, South Korea.
Ui Sup
US
Shin
Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Chang Sik
CS
Yu
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Inchul
I
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003251:Constriction, Pathologic / Q000235:genetics / Q000601:surgery; D003424:Crohn Disease / Q000150:complications* / Q000235:genetics* / Q000601:surgery; D005260:Female; D005838:Genotype; D006801:Humans; D007422:Intestines / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012003:Rectal Fistula / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D012086:Reoperation; D056910:Republic of Korea; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha
Complication; Crohn's disease; Single nucleotide polymorphism; TNFSF15