Autor: |
Sýkora, Josef, Šubrt, Ivan, Dìdek, Petr, Siala, Konrad, Schwarz, Jan, Machalová, Veronika, Varvařovská, Jana, Pazdiora, Petr, Pozler, Oldrich, Stožický, František |
Zdroj: |
Journal of Pediatric Gastroenterology & Nutrition; May 2006, Vol. 42 Issue: 5 p479-487, 9p |
Abstrakt: |
Our pilot study aimed to determine the effect of tumor necrosis factor‐alpha (TNF‐α) 308 G→A promoter single‐nucleotide polymorphism in pediatric inflammatory bowel disease (IBD), its influence on inflammatory activity and the clinical manifestations. 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‐α 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. Significant differences in TNF‐α 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‐α 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‐α 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‐α 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. Although not necessarily dictating IBD initiation, the TNF‐α 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. |
Databáze: |
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