Vitamin D Receptor Gene FOKI Polymorphism Contributes to Increasing the Risk of HIV-Negative Tuberculosis: Evidence from a Meta-Analysis

Xu, Chun Cheng; Tang, Peijun; Ding, Cheng; Li, Chang; Chen, Jun; Xu, Zhenlei; Mao, Yi; M, Wu

doi:10.1371/journal.pone.0140634

Cited by 14 publications

(7 citation statements)

References 37 publications

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“…Indeed, HIV infection is associated with a greater risk for disease than HIV-negative individuals. 57 Of note, a study by Xu et al 58 also focused on this topic; nevertheless, our study is more comprehensive than this study and we found the risk effect only in HIV-negative TB patients but not observed in HIV-positive or not clearly identified group. Therefore, our results suggest it is crucial to avoid selection bias in such genotype association studies.…”

Section: Discussioncontrasting

confidence: 56%

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis

et al. 2015

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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 (I2 = 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; I2 = 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; I2 = 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; I2 = 0.0%, and P = 0.740 for heterogeneity) and African group (OR = 0.99, 95% CI = 0.726–1.341, P = 0.934; I2 = 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.

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Section: Discussioncontrasting

confidence: 56%

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis

et al. 2015

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“…As demonstrated above, meta-analyses are often used to address inconsistencies among studies. For example, meta-analyses demonstrated an association of a polymorphism in VDR in HIV-negative TB patients (Huang et al 2015 ; Xu et al 2015 ). However, even results from meta-analyses can be mixed, particularly for HLA-DRB1 , with some alleles conferring protection and others susceptibility depending on the population studied (Tong et al 2015 ; Yang et al 2016 ).…”

Section: Host Genetic Susceptibility To Bacterial Infectionmentioning

confidence: 99%

Inter-individual variation in health and disease associated with pulmonary infectious agents

2018

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Respiratory infectious diseases resulting from bacterial or viral pathogens such as Mycobacterium tuberculosis, Streptococcus pneumoniae, respiratory syncytial virus (RSV), or influenza, are major global public health concerns. Lower respiratory tract infections are leading causes of morbidity and mortality, only behind ischemic heart disease and stroke (GBD 2015 LRI Collaborators in Lancet Infect Dis 17(11):1133–1161, 2017). Developing countries are particularly impacted by these diseases. However, while many are infected with viruses such as RSV (> 90% of all individuals are infected by age 2), only sub-populations develop severe disease. Many factors may contribute to the inter-individual variation in response to respiratory infections, including gender, age, socioeconomic status, nutrition, and genetic background. Association studies with functional single nucleotide polymorphisms in biologically plausible gene candidates have been performed in human populations to provide insight to the molecular genetic contribution to pulmonary infections and disease severity. In vitro cell models and genome-wide association studies in animal models of genetic susceptibility to respiratory infections have also identified novel candidate susceptibility genes, some of which have also been found to contribute to disease susceptibility in human populations. Genetic background may also contribute to differential efficacy of vaccines against respiratory infections. Development of new genetic mouse models such as the collaborative cross and diversity outbred mice should provide additional insight to the mechanisms of genetic susceptibility to respiratory infections. Continued investigation of susceptibility factors should provide insight to novel strategies to prevent and treat disease that contributes to global morbidity and mortality attributed to respiratory infections.

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“… 5 , 6 A recent meta-analysis suggested that VDR FokI polymorphism contributes to increasing the risk of pulmonary tuberculosis in human immunodeficiency virus-negative individuals, especially in the Asian region. 7 FokI polymorphism in VDR gene has also been shown to be associated with the susceptibility to spinal tuberculosis in Chinese Han population. 8 We selected VDR ApaI and TaqI genes, for our study, because both these genes are relatively less well studied in spinal tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

25-Hydroxy Vitamin D, Vitamin D Receptor and Toll-like Receptor 2 Polymorphisms in Spinal Tuberculosis

et al. 2016

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Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such asTLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated serum vitamin D, and VDR and TLR-2 gene polymorphisms in patients with spinal tuberculosis.This study comprised of 3 groups: spinal tuberculosis, pulmonary tuberculosis, and controls (each with 106 subjects). Enzyme-linked immunosorbent assay was used to measure vitamin D levels, and polymerase chain reaction-sequencing method was used to analyze VDR and TLR-2 gene polymorphisms. Patients were followed up for 6 months.Vitamin D deficiency was significantly more prevalent in patients with spinal tuberculosis (P < 0.001) and pulmonary tuberculosis (P = 0.011), versus controls. The heterozygous and mutant genotypes of VDR TaqI gene were significantly associated with spinal tuberculosis (P < 0.001; odds ratio [OR] 4.74 [2.45–9.18]) and pulmonary tuberculosis (P < 0.001; OR 3.52 [1.80–6.88]) when compared with controls. The heterozygous and mutant variants of VDR ApaI gene were significantly more common in patients with spinal tuberculosis in comparison with patients with pulmonary tuberculosis (P < 0.001; OR 2.90 [1.65–5.10]) and controls (P < 0.001; OR 6.56 [3.41–12.61]). We did not observe any significantly different results for TLR-2 gene polymorphisms. Vitamin D deficiency, VDR, and TLR-2 polymorphisms did not affect the 6-month disability.Vitamin D deficiency and VDR gene polymorphisms are significantly more prevalent in people with pulmonary and spinal tuberculosis. They may, in isolation or collectively, confer susceptibility to pulmonary and spinal tuberculosis.

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Vitamin D Receptor Gene FOKI Polymorphism Contributes to Increasing the Risk of HIV-Negative Tuberculosis: Evidence from a Meta-Analysis

Cited by 14 publications

References 37 publications

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis

Inter-individual variation in health and disease associated with pulmonary infectious agents

25-Hydroxy Vitamin D, Vitamin D Receptor and Toll-like Receptor 2 Polymorphisms in Spinal Tuberculosis

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