Inflammatory Bowel Disease
Subject Category: Inflammatory Bowel Disease
Am J Gastroenterol 2009; 104:384–391; doi:10.1038/ajg.2008.36; published online 13 January 2009
TNFSF15 Polymorphisms Are Associated With Susceptibility to Inflammatory Bowel Disease in a New European Cohort
R Thiébaut1, S Kotti PhD2, C Jung MD1, F Merlin1, J F Colombel MD, PhD3, M Lemann MD, PhD4, S Almer MD, PhD5, C Tysk MD, PhD6, M O'Morain MD, PhD7, M Gassull MD, PhD8, V Binder MD, PhD9, Y Finkel MD, PhD10, L Pascoe PhD11 and J-P Hugot MD, PhD1,12
- 1INSERM, U843, Hôpital Robert Debré, Université Paris Diderot, Paris, France
- 2INSERM, U535, Université Paris-sud, Villejuif, France
- 3Registre EPIMAD, Service d'Epidémiologie et de Santé Publique, Hôpital Calmette, Lille, France
- 4Groupe d'Etude Thérapeutiques des Affections Inflammatoires Digestives, Service de Gastroentérologie, Hopital Saint Louis, Paris, France
- 5Division of Gastroenterology and Hepatology, Institutionen för Klinisk och Experimentell Medicin, Linköpings Universitet, Linköping, Sweden
- 6Department of Gastroenterology, School of Health and Medical Sciences, Örebro University Hospital, Örebro University, Örebro, Sweden
- 7Department of Gastroenterology, Adelaide and Meath Hospital, Dublin, Ireland
- 8Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
- 9Department of Gastroenterology, Herlev Hospital, Herlev, Denmark
- 10Department of Gastroenterology, Karolinska Children's Hospital, Stockholm, Sweden
- 11Fondation Jean Dausset, CEPH, Paris, France
- 12Assistance Publique Hôpitaux de Paris, Service de Gastroentérologie Pédiatrique, Hôpital Robert Debré, Paris, France
Correspondence: J.-P. Hugot, MD, PhD, Service de Gastroentérologie Pédiatrique, Hôpital Robert Debré, 48 Bd Sérurier, Paris 75019, France. E-mail: jean-pierre.hugot@rdb.aphp.fr
Received 31 March 2008; Accepted 3 September 2008; Published online 13 January 2009.
Abstract
OBJECTIVES:
Infl ammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD.
METHODS:
A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied.
RESULTS:
The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05–1.50)) and CD (P=0.02) (OR=1.31 (1.03–1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A.
CONCLUSIONS:
This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.
