Original Contribution
The American Journal of Gastroenterology (2005) 100, 1598–1604; doi:10.1111/j.1572-0241.2005.41737.x
TNF Promoter Polymorphisms and Modulation of Growth Retardation and Disease Severity in Pediatric Crohn's Disease
Arie Levine MD1, Raanan Shamir MD2, Eytan Wine MD1, Batya Weiss MD3, Amir Karban MD4, Ron R Shaoul MD5, Shimon S Reif MD6, Benjamin Yakir PhD7, Marcello Friedlander PhD8, Yael Kaniel MD9 and Esther Leshinsky-Silver PhD9
- 1Pediatric Gastroenterology and Nutrition Unit, E. Wolfson Medical Center, Holon, Israel and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
- 2Pediatric Gastroenterology and Nutrition Units, Meyer Children's Hospital, Haifa, Israel;
- 3Tel-Hashomer Medical Center, Tel Aviv, Israel and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
- 4Gastroenterology Division, Rambam Medical Center, Haifa, Israel;
- 5Bnei Zion Medical Center, Haifa, Israel;
- 6Dana Children's Hospital, Tel Aviv, Israel and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
- 7Department of statistics, Hebrew University, Jerusalem, Israel;
- 8Daniel Biotech Weizman, Science Park Rehovot, Israel;
- 9Molecular Genetics Laboratory, E. Wolfson Medical Center, Holon, Israel
Correspondence: Arie Levine, MD, Director Pediatric Gastroenterology Service, E. Wolfson Medical Center, PO Box 5 Holon, Israel 58100
Received 30 October 2004; Revised 0000; Accepted 24 January 2005.
Abstract
OBJECTIVES:
Delayed growth is common in pediatric Crohn's disease (CD). Multiple factors have been shown to affect growth in this situation, the most prominent being the presence and severity of inflammation and inadequate nutritional intake. Inflammation, anorexia, and weight loss are all manifestations of circulating TNF-alpha, which is elevated in CD. The ability to secrete TNF-alpha may be affected by polymorphisms in the TNF-alpha promoter. The aim of our study was to determine whether growth retardation and disease severity in pediatric onset CD are affected by TNF promoter genotype.
METHODS:
Genotyping for TNF-alpha and NOD2/CARD15 single nucleotide polymorphisms was performed in 87 patients with detailed growth records. Parameters including disease location and disease severity were recorded, and the effect of these polymorphisms on Z-scores for height and weight at disease onset and during follow-up were analyzed.
RESULTS:
Lower age of onset was linked to more height retardation, while the presence of colonic disease and the absence of ileal disease were more likely to predict the absence of growth retardation. The presence of two polymorphisms thought to decrease circulating TNF-alpha was associated with higher mean Z-scores for height and a trend toward less growth retardation. Two other polymorphisms were modestly associated with disease severity.
CONCLUSION:
Polymorphisms in the TNF-alpha promoter may independently modulate growth and disease severity in pediatric onset CD. The effect of these polymorphisms does not appear to be mediated via weight loss, and is relatively modest.
