Avaliação de variantes de base única (SNVs) em receptores da vitamina D (VDR) em pacientes com tuberculose

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains one of the major global public health challenges, with high incidence rates particularly in regions such as Northern Brazil. In 2024, the state of Amazonas recorded the highest national incidence rate, with 94.7 cases per 100,000 inhabitants. Susceptibility to TB is influenced by social, environmental, and genetic factors, with vitamin D and its receptor (VDR) recognized as important modulators of the immune response to infection. This study aimed to investigate the association between single nucleotide variants (SNVs) in the VDR gene and the occurrence of pulmonary tuberculosis. A total of 640 individuals were included, comprising 321 patients and 319 controls, genotyped by qPCR for the SNVs rs2228570, rs7975232, rs731236, and rs1544410. The rs2228570 variant showed a significant association under the log-additive model (p = 0.046; OR = 1.26; 95% CI = 1.01–1.57), suggesting increased risk with higher frequency of the A allele. A significant protective effect was observed for rs731236 (dominant model: p = 0.012; OR = 0.67; 95% CI = 0.49–0.92) and rs1544410 (recessive model: p = 0.0002; OR = 0.33; 95% CI = 0.18–0.61), with the G and T alleles, respectively, associated with reduced disease risk. In contrast, the rs7975232 variant showed no significant association with TB in the tested models. Haplotype analysis revealed that the combination ACCA was significantly associated with increased TB risk (p = 0.0099), whereas the GATG haplotype was associated with a protective effect (p = 0.0151). Additionally, 25(OH)D quantification indicated hypovitaminosis D in a substantial proportion of individuals, with lower concentrations observed in TB patients. These findings reinforce the potential role of vitamin D and VDR gene variants in TB immunoregulation and contribute to the understanding of genetic susceptibility to the disease in a highly endemic population. Such evidence may guide future research on genetic biomarkers and modifiable risk factors in similar settings.