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

Murugesan, Harishankar and Muthukumaran, Dhanyaa and Paramasivam, Selvaraj and Sampath, Pavithra and Ramamurthy, Karthikeyan and Veerasamy, Athikesavan and Muralitharan, Aarti and Ranganathan, Uma Devi and Bethunaickan, Ramalingam (2025) Association of CYP27B1 promoter gene variants of vitamin D pathway with pulmonary tuberculosis and vitamin D levels. Association of CYP27B1 promoter gene variants of vitamin D pathway with pulmonary tuberculosis and vitamin D levels, 221 (109656). pp. 1-8.

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Abstract

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.

Affiliation:	ICMR- National Institute for Research in Tuberculosis
Item Type:	Article
URI:	http://eprints.nirt.res.in/id/eprint/2093

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