Association between IL12B polymorphisms and tuberculosis risk: a meta-analysis

The interleukin (IL) 12B gene encodes p40, the subunit of both IL-12 and IL-23, which are important regulators of the type I T helper cell (TH1) immune response. IL12B 3' UTR and promoter polymorphisms have been reported to be correlated with IL-12 p40 production and have been suggested to be associated with TB (tuberculosis) susceptibility. Studies that have investigated the associations between these polymorphisms and TB risk have reported conflicting results. In this study, we performed a meta-analysis with 11 case-control studies (2897 cases/2653 controls) for the IL12B 3' UTR polymorphism and four case-control studies (1037 cases/1126 controls) for the IL12B promoter polymorphism to explore a more precise estimate of these associations. Crude odds ratios with 95% confidence intervals were assessed for the association using fixed- and random-effects models. For the IL12B 3' UTR variant, no significant associations were observed in genotypic and allelic tests in the overall analysis. A stratified analysis by ethnicity showed a significant association in Caucasians in dominant model models AC+CC vs. AA (OR=0.69, 95% CI: 0.51-0.93, p=0.015, P(heterogeneity) = 0.818). The allelic contrast indicated significant effects of the C allele on TB risk in Caucasians (OR=0.74, 95% CI: 0.58-0.95, p=0.019, P(heterogeneity) = 0.377), whereas such effects were not observed in Asians or in Africans. For the IL12B promoter variant, no significant associations were observed in either genotypic or allelic tests with the limited data that were available. This meta-analysis suggests that the C allele of the IL12B 3' UTR may act as a TB risk factor in Caucasians but not in Asians or in Africans. The effect of IL12B polymorphisms on TB risk might be influenced by ethnicity. To further confirm our findings, well-designed studies with large sample sizes and representing different ethnicities are required.