Abstract
The relationship of four potentially functional polymorphisms of the vitamin D receptor (VDR) gene, ApaI, BsmI, FokI and TaqI , with tuberculosis susceptibility were considered. The aim of this meta-analysis was to explore the association between the four polymorphisms and tuberculosis risk in different ethnic backgrounds. Eligible case-control studies that were catalogued before April 1st 2013 were enrolled, and the heterogeneity between the studies was evaluated using a χ2 based Q-test. Fixed and random effect models were built to evaluate the association of the four polymorphisms with the risk of tuberculosis, and the association between the four polymorphisms and tuberculosis was expressed as the odds ratio (OR) and 95% confidence interval (CI). Finally, twenty nine qualified studies were enrolled for this meta-analysis that included 6179 tuberculosis cases and 6585 healthy controls. The variant homozygote genotype of the FokI polymorphism was associated with a significantly increased risk of tuberculosis when compared to the heterozygote and wild type homozygote genotypes in the Chinese population (ff vs. Ff+FF: ORrecessive=1.97, 95%CI: 1.32-2.93, P bonferroni=0.0032; heterogeneity test: χ2=0.24, P=0.62). For European subjects, the homozygote and heterozygote genotypes of the BsmI polymorphism were associated with a significantly decreased risk of tuberculosis when compared to the wild type homozygote (bb+Bb vs. BB: ORdominant=0.41, 95%CI, 0.22-0.76, P bonferroni=0.02; heterogeneity test: χ2=2.59, P=0.11). Based on the above results, we conclude that variants of the VDR gene that are homozygous for the FokI polymorphism might be more susceptible to tuberculosis in Chinese. Furthermore, larger sample studies are warranted to confirm the protective effects of BsmI variants on tuberculosis in the Europeans.
Highlights
Several studies have revealed that a deficiency of vitamin D would increase the risk of tuberculosis [1,2], and vitamin D from food or exposure to sunlight would benefit the treatment of tuberculosis [3,4,5]. 1,25-dihydroxyvitamin D3, which is the active form of vitamin D, was activated by 1α-hydoxylase that was expressed by macrophages and other immune cells and bind to the vitamin D receptor (VDR) for to modulate the immune system in fighting with Mycobacterium infection [6].In recent years, the anti-bacteria effects of Vitamin D in the human immune system have been explored extensively [7]
Two medical subject headings (Mesh), “Tuberculosis” and “Vitamin D receptor”, were used to search for related articles, and qualified articles were included according to the following criteria: (1) the original articles were published in English; (2) the studies had a case-control design and were conducted in human beings; and (3) the articles contained available genotyping information on VDR gene polymorphisms (ApaI, BsmI, FokI and TaqI were the four single nucleotide polymorphisms (SNPs) that were analyzed in this article)
The Horbold-Egger’s test supported the result of Egger’s test that suggested that the publication bias induced by small sample sizes was limited (t=0.48, P=0.633). In this meta-analysis of the relationship between the VDR gene polymorphisms and the risk of tuberculosis, we found that the FokI SNP in the recessive model significantly increased the risk of tuberculosis, and the risk effect was found in the Chinese population
Summary
Several studies have revealed that a deficiency of vitamin D would increase the risk of tuberculosis [1,2], and vitamin D from food or exposure to sunlight would benefit the treatment of tuberculosis [3,4,5]. 1,25-dihydroxyvitamin D3, which is the active form of vitamin D, was activated by 1α-hydoxylase that was expressed by macrophages and other immune cells and bind to the vitamin D receptor (VDR) for to modulate the immune system in fighting with Mycobacterium infection [6].In recent years, the anti-bacteria effects of Vitamin D in the human immune system have been explored extensively [7]. The VDR gene is located in the chromosomal 12q13 region, and, in the last decade, studies have focused on the association between genetic variants of the VDR gene and tuberculosis risk based on the hypothesis that genetic alterations of the VDR gene might lead to important defects in gene activation, that could affect immune function. Four potentially functional single nucleotide polymorphisms (SNPs) of the VDR gene (ApaI, SNP ID: rs7975232; BsmI, SNP ID: rs1544410; FokI, SNP ID: rs2228570; and TaqI, SNP ID: rs731236) have been main focus in relation to the risk of tuberculosis compared to other SNPs. Changes in the amino acid sequence or transcriptional activity might be induced by these four mutations; these mutations could affect an individual’s susceptibility to tuberculosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
