Vitamin D receptor gene variations and tuberculosis susceptibility: Insights from Indonesian populations

Pulmonary tuberculosis (PTB) remains a major global health challenge, with Indonesia bearing a substantial disease burden. Genetic predisposition, particularly vitamin D receptor (VDR) gene polymorphisms, has been implicated in PTB susceptibility. However, findings remain inconsistent across populations. This study examines the association of four VDR polymorphisms (FokI, ApaI, BsmI, and TaqI) with PTB susceptibility in three Indonesian ethnic groups, while also evaluating sociodemographic and lifestyle risk factors.

A case-control study was conducted among 267 participants from Makassar, Bugis, and Toraja ethnic groups in South Sulawesi, Indonesia. Participants were categorized into active PTB (n= 88), latent PTB, and healthy control groups. Genotyping of VDR polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism. Sociodemographic factors, smoking habits, alcohol consumption, and education levels were recorded. Statistical analyses included chi-squared tests, logistic regression for odds ratio (OR) calculations, and receiver operating characteristic (ROC) curve analysis to assess the discriminatory power of genetic markers (AUC values). The optimal diagnostic threshold was determined using the Youden index.

The FokI CC genotype was significantly associated with PTB risk (p= 0.014; OR= 2.12, 95% CI: 1.18-3.79), whereas the TT genotype showed a protective effect. The ApaI TT genotype also exhibited a strong association with PTB susceptibility (p< 0.001; OR= 2.65, 95% CI: 1.63-4.29). No significant associations were found for BsmI and TaqI polymorphisms. Sociodemographic analysis revealed that lower education levels and smoking significantly increased PTB risk (p= 0.006 and p= 0.011, respectively). ROC analysis for combined FokI CC and ApaI TT genotypes yielded an AUC of 0.76 (95% CI: 0.68-0.84), demonstrating moderate predictive power.

This study highlights the multifactorial nature of PTB susceptibility, emphasizing the role of VDR gene polymorphisms, education, and lifestyle factors. The findings support the integration of genetic screening into PTB risk assessment and underscore the need for targeted public health interventions in genetically diverse populations.