Abstract
BackgroundGenetic 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 FindingsWe 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.ConclusionsThis meta-analysis suggests that VDR BsmI gene polymorphism is associated with a significant decreased TB risk, especially in Asian population.
Highlights
According to the latest information of the tuberculosis (TB) epidemic provided by the World Health Organization (WHO) Global Tuberculosis Report 2012, the TB mortality and incidence rates have been decreasing for several years
This meta-analysis suggests that vitamin D receptor (VDR) BsmI gene polymorphism is associated with a significant decreased TB risk, especially in Asian population
Multiple candidate genes have been investigated to determine the relationship between single nucleotide polymorphisms (SNPs) and TB risk, including the natural resistance–associated macrophage protein 1 (NRAMP1) gene [7], interleukin (IL) genes [8,9], vitamin D receptor (VDR) genes [10], and tumor necrosis factor (TNF) genes [11]
Summary
According to the latest information of the tuberculosis (TB) epidemic provided by the World Health Organization (WHO) Global Tuberculosis Report 2012, the TB mortality and incidence rates have been decreasing for several years. It is suggested that the susceptibility to TB is influenced by many factors, such as HIV infection, environmental and host genetic factors [3,4,5,6]. There are various studies reporting that host genetic factors may play an important role in susceptibility to TB. Multiple candidate genes have been investigated to determine the relationship between single nucleotide polymorphisms (SNPs) and TB risk, including the natural resistance–associated macrophage protein 1 (NRAMP1) gene [7], interleukin (IL) genes [8,9], vitamin D receptor (VDR) genes [10], and tumor necrosis factor (TNF) genes [11]. Many studies have investigated the association between VDR BsmI gene polymorphism and TB risk, but yielded inconclusive results
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