A meta-analysis on the association between three promoter variants of TNF-α and Crohn’s disease
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, including ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study was to determine the prevalence of the tumor necrosis factor alpha (TNF-α) promoter polymorphisms at positions −238 and −308, and to measure the serum CRP levels in CD and UC patients and in a healthy population. The TNF-α gene polymorphisms were determined by the PCR-RFLP method. Samples of 74 CD and 50 UC patients and 138 healthy Hungarian volunteers were examined. The G→A substitution at position −308 (designated the TNF2 allele) was significantly less frequent among IBD patients than in the control group (P=0.0009); 15% of the CD patients and 18% of the UC patients carried the mentioned allele, which was significantly less frequent compared with the healthy population (33%, P=0.0035 and P=0.036, respectively). No difference in the G→A substitution at position −238 was observed. We found the median CRP levels to be significantly higher in the active phase of the disease than in the inactive phase among the −308A allele carriers (P=0.002), while this difference was not significant when the CRP levels in the active and inactive phases were compared among the −308GG homozygous patients (P=0.084). The decreased frequency of the TNF2 allele (known to be associated with elevated TNF-α production) in IBD may determine the severity of IBD through its interaction with plasma CRP levels, and may modify the pathogenesis of this chronic inflammatory disease.