Effect of the Polymorphism of Tumor Necrosis Factor-alpha-308 G/A Gene Promoter on the Susceptibility to Ulcerative Colitis: A Meta-Analysis

Background: Ulcerative colitis (UC) is a complex polygenic disease in which gene-environment interactions are important. Some studies have reported that proinflammatory polymorphisms in tumor necrosis factor-alpha-308 (TNF-alpha-308) gene promoter (substitution G -> A, designated as TNF1 and TNF2) is associated with increased UC risk. However, the results of individual studies have been inconsistent. Methods: To investigate the inconsistent findings in studies of the association of the polymorphism of TNF-alpha-308 gene promoter with susceptibility to UC, a systematic review of the published data was undertaken and a meta-analysis was performed. The MEDLINE database was searched for case-control studies published in English language journals from 1966 to November 2007. Data were extracted using standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: 15 eligible studies, 7 of Europeans, 2 of Americans, and 6 of Asians including 4 East Asians, were included in the meta-analysis. An association between UC and TNF2 allele was not found in the overall population (OR 1.28, 95% CI 0.84-1.96, p = 0.25). However, stratification by ethnicity indicated that there was significant association between TNF2 allele and UC in East Asians (OR 2.27, 95% CI 1.08-4.77, p = 0.03). Conversely, there was no association between TNF2 allele and UC patients from the European (OR 0.85, 95% CI 0.42-1.71, p = 0.65) and Asian samples (OR 1.64, 95% CI 0.98-2.74, p = 0.06). The OR for the TNF2/2+TNF2/1 genotype versus TNF1/1 genotype in samples overall and in each ethnic group showed a similar trend to those for the TNF2 allele. Conclusion: In East Asians, the TNF2 allele confers a significant risk for developing UC. There is no association between the polymorphism of TNF-alpha-308 gene promoter and UC in Europeans. Copyright (C) 2008 S. Karger AG, Basel