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.