Association of CYP27B1 promoter gene variants of vitamin D pathway with pulmonary tuberculosis and vitamin D levels

Cyp27b1 polymorphisms are stated to be associated with different diseases including tuberculosis (TB). Since the gene variants located in the promoter region may have a significant influence on gene transcription/translation and Cyp27b1 enzyme is involved in critical steps in vitamin D metabolism, we aim to study whether Cyp27b1 gene promoter variants namely −1077 (C/G), −1260 (C/A) and the region immediately 5′ to the promoter −1918 (C/T) have any linkage with pulmonary tuberculosis risk/defence and to determine their influence on vitamin D level in normal healthy controls (HCs) and pulmonary tuberculosis (PTB) patients of the South Indian population. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method were used to genotype the genomic DNA after it was extracted using the salting-out approach. The Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure the amount of vitamin D. In the co-dominant model, a significant association was detected with TB liability in the −1077 “GG” genotype [Odds ratio (OR): 2.10(1.18–3.73); p = 0.015]. In addition, a noteworthy linkage was detected with TB protection in the dominant model [GG vs CG + CC, OR: 0.40(0.21–0.75); p = 0.0035]. In the −1918 (C/T) variant, a substantial linkage was detected in the heterozygous −1918 “CT” genotype with TB risk [OR: 1.90 (1.05–3.44); p = 0.046] in co-dominant model, whereas a protective linkage was detected in less recurrent “TT” genotype [OR: 0.42 (0.19–0.94); p = 0.049] with TB. Furthermore, those risky genotypes are substantially linked with more TB risk in males than females. Strong links between −1077 and −1260 variations were revealed by haplotype analysis, and its haplotypes “GC” (−1077G, −1260C) were found to be significantly associated with increased TB risk. Vitamin D deficiency (<20 ng/ml) was detected at a higher frequency in PTB patients than HCs in −1077 “GG”, −1260 “CA” and −1918 “CT” risky genotypes. This needs to be confirmed by bigger sample sizes in future research.