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.

FIGURE 1

Flow diagram of included studies for this meta-analysis.

FIGURE 2

Forest plot for the association between FokI polymorphisms and TB risk stratified by ethnicity in recessive model (ff vs fF+FF).

FIGURE 3

Forest plot for the association between FokI polymorphisms and TB riskstratified by HIV status in recessive model (ff vs fF+FF).

FIGURE 4

Galbraith plot analysis to evaluate heterogeneity: Rathored et al and Wu et al were the outlier studies in recessive model (ff vs fF+FF).

FIGURE 5

Funnel plot for studies of the association between in recessive model (ff vs fF+FF). The horizontal and vertical axes correspond to the OR and 95% CI. CI = confidence interval; OR = odds ratio.