Association of rs7041 and rs4588 polymorphisms of vitamin D binding protein gene in pulmonary tuberculosis

Abstract Vitamin D deficiency is often associated with tuberculosis susceptibility. Variants of vitamin D binding protein gene are reported to be associated with blood circulating concentration of 25(OH)D levels. Objectives: The aim of the present study was to understand the association of rs7041 (G/T) and rs4588 (C/A) polymorphisms with tuberculosis susceptibility/protection in 125 Healthy controls (HCs) and 125 pulmonary tuberculosis (PTB) patients and to understand whether the gene variants have any influence on 25(OH)D levels in South Indian population. The genotyping for both the polymorphisms were done by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) method. 25(OH)D levels were estimated by ELISA method. The results revealed that under codominant model, rs4588 ‘CA' genotype significantly associated with TB susceptibility [OR: 1.47 (0.85–2.55); p = 0.049] and associated with 47.4% 25(OH)D deficiency in PTB patients. Whereas, under recessive model (‘AA' vs ‘CC' + ‘CA') rs4588 ‘AA' genotype significantly associated with TB protection [OR: 0.14 (0.02–1.29); p = 0.042]. Whereas in rs7041 polymorphism, under overdominant model (‘TG' vs ‘GG+’TT'), no association was found. Increased 25(OH)D levels were found with rs7041 “GG”, and rs4588 “CC” genotype in HCs and PTB patients. Haplotypes ‘TA' and ‘TC' associated with susceptibility to TB in males compared with females [‘TA' - OR: 4.18 (1.84–9.49); ‘TC' - OR: 3.63 (1.34–9.84)]. The results suggest that the heterozygous genotype rs4588 “CA” significantly associated with susceptibility while rs4588 “AA” genotype significantly associated with TB protection. Gene variants with 25(OH)D deficiency revealed no significant association due to limited sample size. However, in rs7041 “TG” and rs4588 “CA” genotype was associated with 61.1% and 47.4% 25(OH)D deficiency (OR > 2.0) in PTB patients. Future studies with larger sample size are needed to confirm this study finding.