TNF promoter polymorphisms and modulation of growth retardation and disease severity in pediatric Crohn's disease.
OBJECTIVE
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.


CONCLUSIONS
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.
Levine
Arie
A
Pediatric Gastroenterology and Nutrition Unit, E. Wolfson Medical Center, Holon, Israel.
Shamir
Raanan
R
Wine
Eytan
E
Weiss
Batya
B
Karban
Amir
A
Shaoul
Ron R
RR
Reif
Shimon S
SS
Yakir
Benjamin
B
Friedlander
Marcello
M
Kaniel
Yael
Y
Leshinsky-Silver
Esther
E
D000225:Adenine; D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D003424:Crohn Disease / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D003596:Cytosine; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000209:etiology* / Q000503:physiopathology*; D006147:Guanine; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D013941:Thymine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine