Cytokine Tumor Necrosis Factor-alpha A Promoter Gene Polymorphism at Position -308 G-->A and Pediatric Inflammatory Bowel Disease: Implications in Ulcerative Colitis and Crohn's Disease.

摘要

OBJECTIVES:: Our pilot study aimed to determine the effect of tumor necrosis factor-alpha (TNF-alpha) 308 G-->A promoter single-nucleotide polymorphism in pediatric inflammatory bowel disease (IBD), its influence on inflammatory activity and the clinical manifestations. METHODS:: We obtained genomic DNA from 164 subjects, 82 with long-standing IBD aged 8 to 18 years: 46 with Crohn disease (CD) and 36 with ulcerative colitis (UC). Eighty-two healthy children served as the control population. Genotyping was determined by using a restriction enzyme-based assay. TNF-alpha 308 G-->A polymorphism was assessed in terms of inflammatory (C-reactive protein [CRP]) and disease activity. The latter was assessed by the Pediatric Crohn's Disease Activity Index (PCDAI) and the Truelove index for CD and UC, respectively. RESULTS:: Significant differences in TNF-alpha 308 A polymorphism were found between the IBD group and controls (P < 0.05) and the UC group and controls (P < 0.001). No differences were noted between TNF-alpha 308 A polymorphism and clinical characteristics in UC. The frequency of the -308 A allele of TNF was not different in CD compared with that in the control group. The frequency of TNF-alpha 308 A genotype was significantly higher in CD patients with predominantly stenosing/penetrating disease compared with patients without complications (P < 0.001) and healthy controls (P < 0.01). In CD patients, those carrying TNF -308 A had a significant increase in CRP (P < 0.05) and the PCDAI (P < 0.05). In CD, CRP levels strongly correlated with the PCDAI (r 0.6150, P < 0.001). In UC, significant differences among the mean levels of CRP (P < 0.05) and disease activity (P < 0.001) related to TNF-alpha 308 A polymorphism were found. Allele distribution (odds ratio, 12.9; CI, 1.18-140.81, P < 0.001) and CRP serum levels (odds ratio, 1.020; CI, 1.00-1.04, P < 0.001) were independently associated with CD complications. CONCLUSIONS:: Although not necessarily dictating IBD initiation, the TNF-alpha 308 A polymorphism may play a role in modifying the CD phenotype. The polymorphism may influence disease activity as well as more intense inflammatory activity in both forms of IBD and may modify the progression of chronic digestive tract inflammation.