TNF PROMOTER POLYMORPHISMS MODULATE GROWTH RETARDATION AND DISEASE SEVERITY IN PEDIATRIC CROHN??S DISEASE

Abstract

Background and Aims: 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 presence and severity of inflammation and inadequate nutritional intake. Inflammation, anorexia and weight loss may 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 Crohn's disease are affected by TNF promoter genotype. Methods: Genotyping for TNF alpha single nucleotide polymorphisms (SNPs) was performed in 87 patients with detailed growth records. Parameters including disease location, disease severity and were recorded, and the effect of these polymorphisms on z-scores for height and weight at disease onset and during follow-up until age 16 for height and 18 for weight were analyzed. Results: Z scores for height <1 S.D. occurred in 44% of patients, <2 SD in 19%. Lower age of onset was linked to more height retardation, while presence of colonic disease and absence of ileal disease were more likely to predict absence of growth retardation (p = 0.004). Mean height scores were increased with 238 G/A (p = 0.003) while Height retardation was reduced by two polymorphisms reported to decrease circulating TNF(−238 G/A, −863 C/A).The effect on height was not associated with lower z scores for weight. Disease severity was modestly associated with the pro-inflammatory polymorphisms −308 G/A and inversely associated with 857 C/T. Conclusion: Polymorphisms in the TNF alpha promoter may modulate disease severity and growth retardation in pediatric onset CD, though this effect appears to be modest. The effect of genotype on growth retardation is not associated with TNF mediated weight loss.