Dataset Information

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis: An Update Meta-Analysis.

ABSTRACT: The association between vitamin D receptor (VDR) FokI polymorphism and tuberculosis (TB) risk remains a matter of debate. Potential selection bias exists in most studies using HIV-positive TB patients.An update meta-analysis was carried out to derive a more reliable assessment of the association between FokI polymorphisms and TB risk, especially in HIV-negative TB patients. All major databases from inception to June 2015 were searched for all publications that studied the association between FokI polymorphism and TB risk. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated according to the frequencies of genotypes.In total, 32 studies with 4894 cases and 5319 controls were included in this meta-analysis. In the overall analysis, the estimated OR was 1.34 (95% CI=1.091-1.646, P?=?0.005) in the best genetic model (recessive model, ff vs fF+FF) with moderate heterogeneity (I?=?32.2%, P?=?0.043). In the subgroup analysis stratified by HIV status, significant associations were found only in the HIV-negative TB group (OR?=?1.60, 95% CI?=?1.180-2.077, P?=?0.002; I?=?29.5%, and P?=?0.141 for heterogeneity). In the subgroup analysis stratified by ethnicity, significant associations were found in the Asian group (OR?=?1.65, 95% CI?=?1.205-2.261, P?=?0.002; I?=?43.9%, and P?=?0.024 for heterogeneity), but not in the Caucasian group (OR?=?1.09, 95% CI?=?0.762-1.547, P?=?0.649; I?=?0.0%, and P?=?0.740 for heterogeneity) and African group (OR?=?0.99, 95% CI?=?0.726-1.341, P?=?0.934; I?=?43.9%, and P?=?0.024 for heterogeneity).This meta-analysis confirms that VDR FokI polymorphism contributes to the risk of TB, especially in HIV-negative TB patients and in the Asian group. Further studies are required to clarify the role of the FokI polymorphism in HIV-positive TB and in other ethnic groups.

SUBMITTER: Huang L

PROVIDER: S-EPMC4697973 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other

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Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis: An Update Meta-Analysis.

Huang Liling L Liu Cunxu C Liao Guangfu G Yang Xiaobing X Tang Xiuwen X Chen Jingjie J

Medicine 20151201 51

The association between vitamin D receptor (VDR) FokI polymorphism and tuberculosis (TB) risk remains a matter of debate. Potential selection bias exists in most studies using HIV-positive TB patients.An update meta-analysis was carried out to derive a more reliable assessment of the association between FokI polymorphisms and TB risk, especially in HIV-negative TB patients. All major databases from inception to June 2015 were searched for all publications that studied the association between Fok ...[more]

PMID: 26705207

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Project description:The FokI vitamin D receptor (VDR) polymorphism results in different translation initiation sites on VDR. In the VDRff variant, initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein of 427 amino acids. Conversely, in the VDRFF variant, translation begins at the second ATG site, resulting in a truncated protein with three less amino acids. Epidemiological studies have paradoxically implicated this polymorphism with increased breast cancer risk. 1?,25 (OH)(2)D(3), the active metabolite of vitamin D, is known to inhibit cell proliferation, induce apoptosis and potentiate differentiation in human breast cancer cells. It is well documented that 1?,25 (OH)(2)D(3) downregulates estrogen receptor ? expression and inhibits estrogen mediated signaling in these cells. The functional significance of the VDR FokI polymorphism in vitamin D action is undefined.To elucidate the functional role of FokI polymorphism in breast cancer, MCF-7-Vector, MCF-7-VDRff and MCF-7-VDRFF stable cell lines were established from parental MCF-7 cells as single-cell clones. In response to 1?,25 (OH)(2)D(3) treatments, cell growth was inhibited by 60% in VDRFF cells compared to 28% in VDRff cells. The induction of the vitamin D target gene CYP24A1 mRNA was 1.8 fold higher in VDRFF cells than in VDRff cells. Estrogen receptor-? protein expression was downregulated by 62% in VDRFF cells compared to 25% in VDRff cells. VDR protein stability was greater in MCF-7-VDRFF cells in the presence of cycloheximide. PCR array analyses of VDRff and VDRFF cells revealed increased basal expression levels of pro-inflammatory genes Cyclooxygenase-2, Interleukin-8 and Chemokine (C-C Motif) Ligand 2 in MCF-7-VDRff cells by 14, 52.7 and 5 fold, respectively.These results suggest that a VDRff genotype may play a role in amplifying aggressive breast cancer, paving the way for understanding why some breast cancer cells respond inefficiently to vitamin D treatment.

Dataset Information

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis: An Update Meta-Analysis.

Publications

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis: An Update Meta-Analysis.

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