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

• Published in: Gene 2024-11, Vol.927, p.148679, Article 148679
• Main Authors: Murugesan, Harishankar, Sampath, Pavithra, A., Vamsi Kumar, R., Srividhya, Veerasamy, Athikesavan, Ranganathan, Uma Devi, Paramasivam, Selvaraj, Bethunaickan, Ramalingam
• Format: Article
• Language: English
• Subjects: CYB27B1 gene polymorphism; Genetic susceptibility to TB; Mycobacterium tuberculosis; Tuberculosis; Vitamin D
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2024.148679

•rs118204012 “AA” genotype is significantly associated with susceptibility to tuberculosis.•rs118204012 “AG” and “GG“ genotypes significantly associated with TB protection.•Males are associated with higher TB risk than females.•Vitamin D insufficiency was found higher in rs118204012 “AA” genotype positive patients. 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 D3 by hydroxylation of 25(OH)D3.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. 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). 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 (