Rongshan Tao ^1,2 Shujuan Xiao ³ Lianping Wang ^4,5 Huiqin Suo ⁶ Ruiyu Long ^1,2 Hangyu Liu ⁶ Wei Luo ⁷ Qingjie Li ^8* Feng Hong ^1,2*

• ¹ School of Public Health, Guizhou Medical University, Guiyang, Guizhou Province, China
• ² Key Laboratory of Environmental Pollution Monitoring and Disease Control, Guizhou Medical University, Guiyang, Guizhou Province, China
• ³ Xiangya School of Public Health, Central South University, Changsha, China
• ⁴ School of Traditional Chinese Medicine Jilin Agricultural Science and Technology University, Changchun, China
• ⁵ School of Life Sciences, Jilin University, Changchun, Jilin Province, China
• ⁶ School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
• ⁷ Office of Infection Control, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
• ⁸ Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China

Tuberculosis (TB) is the leading cause of mortality worldwide. Previous studies have reported that TB susceptibility can be caused by vitamin D deficiency, which is affected by polymorphisms in the vitamin D receptor (VDR) gene. However, these results have been inconsistent. Therefore, we performed a meta-analysis to investigate the association between VDR polymorphisms and TB susceptibility. For this, we systematically searched for relevant literature in PubMed, Embase, and Medline databases through December 31 st , 2022. Inclusion and exclusion criteria were made to ensure that HIV-negative population is the targeted subjects. The pooled odds ratio (OR) and 95% confidence interval (CI) were then used to assess the strength of the association, and the quality of the included articles was evaluated using the Newcastle-Ottawa Scale. Potential sources of heterogeneity were evaluated based on subgroup and meta-regression analyses. In our meta-analysis, we found that the FokI polymorphism in the VDR gene was associated with increased TB susceptibility in the allele and recessive genotype models (OR f vs. F = 1.235, 95%CI: 1.035-1.475; OR ff vs. Ff+FF = 1.317, 95%CI:1.005-1.727. Further subgroup analysis based on ethnicity demonstrated the association with the risk of TB in all genotype models of the FokI polymorphism for Han population. Meta-regression analysis also indicated that ethnicity could be a potential source of heterogeneity in the FokI and BsmI polymorphisms in the VDR gene. However, publication year was another source of heterogeneity for the TaqI polymorphism. In summary, the FokI polymorphism in the VDR gene was found to increase the risk of TB in the HIV-negative population, both overall and in Asian populations. The findings presented in this paper could provide clues for preventing TB from the perspective of vitamin D supplementation, which is a controversial topic in the field of medicine and health.