Vitamin D status, VDR and TLR polymorphisms and pulmonary tuberculosis epidemiology in Kazakhstan

Tuberculosis (TB) and vitamin D deficiency remain major public health problems in Kazakhstan. Due to the high incidence of pulmonary tuberculosis in the country and based on the importance of vitamin D in the modulation of the immune response and the association of its deficiency with many health conditions, our research aimed to study the vitamin D status, VDR, and TLR gene polymorphisms, and pulmonary tuberculosis epidemiology in Kazakhstan. Methods: A case-control study included 411 individuals diagnosed with pulmonary TB and 686 controls with no family history of pulmonary tuberculosis. Concentrations of serum vitamin D levels were measured by electrochemiluminescence immunoassay. The gene polymorphisms were determined by real-time polymerase chain reaction (PCR) allelic discrimination assay using TaqMan probes. The association between the risk of pulmonary TB and polymorphisms was evaluated using multimodal logistic regression and assessed with the ORs, corresponding to 95% CIs, and the significance level was determined as p < 0.05. Results: 1097 individuals were recruited from 3 different regions of Kazakhstan. Biochemical data showed vitamin D deficiency (25(OH)D < 20 ng/mL) was present in both groups, with the case group accounting for almost 95% and 43.7% in controls. Epidemiological data revealed that socioeconomic factors like BMI <25 (p<0.001), employment (p<0.001), diabetes (p<0.001), and vitamin D deficiency (p<0.001) were statistically different between case and control groups. Logistic regression analysis, adjusted by sex, age, BMI, residence, employment, smoking, alcohol consumption, and diabetes, showed that T/T polymorphism of VDR gene (rs1544410, OR = 1.97, 95% CI: 1.04-3.72, p = 0.034) and A/A polymorphism of TLR8 gene (rs3764880, OR = 2.44, 95% CI: 1.20-4.98, p = 0.0098) were associated with a high risk of developing pulmonary tuberculosis. Conclusion: Vitamin D deficiency is prevalent in our study cohort and associated with TB progression. Socioeconomic determinants like unemployment, BMI under 25, and diabetes are the main risk factors for developing pulmonary TB in our study. A/A polymorphism of TLR8 (rs3764880) and T/T polymorphism (BsmI, rs1544410) of VDR genes may act as a biomarker for pulmonary tuberculosis in the Kazakh population.