Association of CYP27B1 gene polymorphisms with pulmonary tuberculosis and vitamin D levels

Background and objectives Genetic factors are reported to be connected with tuberculosis (TB) infection. Studies have shown that genetic variations in genes involved in the vitamin D pathway influence the levels of vitamin D found in the bloodstream (serum). Cyp27b1 (1α-hydroxylase) is an enzyme that activates the synthesis of bioactive vitamin D 3 by hydroxylation of 25(OH)D 3. The in vitro studies reported rare gene variants of Cyp27b1 such as rs118204011 and rs118204012, associated with loss of Cyp27b1 function and lower serum vitamin D levels. Globally, a critical gap exists in understanding the link between these gene variants with TB and vitamin D levels. Hence, the study objective is to comprehend the association of Cyp27b1 rs118204009 (G/A), rs118204011 (C/T), and rs118204012 (A/G) with tuberculosis susceptibility/protection and to assess the influence of gene variants on vitamin D levels in both healthy controls (HCs) and those with pulmonary tuberculosis (PTB) in South India. Methods Genomic DNA extraction was performed by salting-out procedure and subsequently genotyped through polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Vitamin D level was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Results In rs118204012 (A/G), a substantial association was found with PTB susceptibility in allele 'A' [Odds Ratio (OR): 1.52 (1.02-2.26); p = 0.044] and 'AA' genotype [OR: 1.69 (1.02-2.81); p = 0.040] through the dominant model. Allele 'G' [OR: 0.66 (0.44-0.98); p = 0.044) was found to be associated with protection against TB. Males were associated with increased susceptibility towards TB compared to females in the rs118204011 "CC" [OR: 3.94 (1.94-7.98); p = 0.002] and rs118204012 'AA' [OR: 4.57 (2.13-9.79); p = 0.0001] genotypes. Vitamin D insufficiency ( Conclusion Cyp27b1 rs118204012 'AA' genotype was found to have association with vitamin D insufficiency and TB susceptibility. In terms of gender, our findings suggest that male individuals are correlated with a higher TB risk. This suggest that the gene variants may be involved in the downstream processing of serum Vitamin D levels and its association with the disease.