Association of Vitamin D Receptor BsmI Gene Polymorphism with Risk of Tuberculosis: A Meta-Analysis of 15 Studies

BACKGROUND Genetic variations in vitamin D receptor (VDR) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between VDR BsmI gene polymorphism and TB risk, but yielded inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS We performed a comprehensive meta-analysis of 15 publications with a total of 2309 cases and 3568 controls. We assessed the strength of the association between VDR BsmI gene polymorphism and TB risk and performed sub-group analyses by ethnicity, sample size and Hardy-Weinberg equilibrium (HWE). We found a statistically significant correlation between VDR BsmI gene polymorphism and decreased TB risk in four comparison models: allele model (b vs. B: OR = 0.78, 95% CI = 0.67, 0.89; Pheterogeneity = 0.004), homozygote model (bb vs. BB: OR = 0.61, 95% CI = 0.43, 0.87; Pheterogeneity = 0.001), recessive model (bb vs. Bb+BB: OR = 0.70, 95% CI = 0.56, 0.88; Pheterogeneity = 0.005) and dominant model (bb+Bb vs. BB: OR = 0.77, 95% CI = 0.61, 0.97; Pheterogeneity = 0.010), especially in studies based on Asian population. Sub-group analyses also revealed that there was a statistically decreased TB risk in "small" studies (<500 participants) and studies with PHWE>0.5. Meta-regression and stratification analysis both showed that the ethnicity and sample size contributed to heterogeneity. CONCLUSIONS This meta-analysis suggests that VDR BsmI gene polymorphism is associated with a significant decreased TB risk, especially in Asian population.