CYP2R1 gene polymorphisms in pulmonary tuberculosis


Identification: Bethunaickan-Ramalingam


Description

CYP2R1 gene polymorphisms in pulmonary tuberculosis
Background: The CYP2R1 gene expresses the enzyme 25-hydroxylase, which is involved in the synthesis of major circulating vitamin D metabolite 25hydroxyvitamin D [25(OH)D]. CYP2R1 gene variants have been reported to be associated both with altered 25(OH) D levels and with development of active diseases including tuberculosis (TB).
Aim and Objectives: The aim of the present study was to understand (I) The association of rs10741657 (G/A) and rs2060793(A/G) CYP2R1 gene polymorphisms with tuberculosis susceptibility / protection among 104 Healthy controls (HCs) and 105 pulmonary tuberculosis (PTB) patients and (2) To comprehend the influence of gene variants on circulating 25(OH)D levels within South Indian population.
Methodology: Genomic DNA was used for genotyping by polymerase chain reaction trailed by restriction fragment length polymorphism (PCR-RFLP) method. Plasma samples were used for 25(OH) D level estimation by ELISA method. Results: For rs10741657, applying a dominant model (GG vs AG+AA), "AG" and "AA" genotypes and in rs2060793 applying the over dominant model (GA vs GG+AA), "GA" genotype were found to be significantly associated with protection to pulmonary tuberculosis. Based on sex, rs10741657 "AG" was significantly associated with protection and "GG" was significantly associated with susceptibility to TB in males. A sufficient vitamin D level was found with rs10741657 "AA" and "AG" genotypes, whereas "GG" genotype was associated with 81.8% of vitamin D deficiency in PTB individuals.
Conclusion: In this study, We observed rs10741657 "AG" and "AA" genotypes to be associated with higher 25(OH)D levels and conferred protection to TB. The lower 25(OH)D levels were associated with rs10741657 "GG" genotype individuals and they may be recommended for vitamin D supplementation for better treatment outcomes.. Further studies with large sample size are needed to confirm the study findings.

Murugesan Harishankar1 , Pavithra Sampath1 , Madhuvanthi Sriram1 , Rajagopalan Raghuraman1 , Veerasamy Athikesavan1 , Ponnuraja Chinnayan2, Banurekha Velayutham3 , Udaykumar Putcha4 , Srikanth Prasad Tripathy5 , Uma Devi Ranganathan1 , Paramasivam Selvaraj1 and Ramalingam Bethunaickan1,4,
1. Department of Immunology, ICMR- National Institute for Research in Tuberculosis, Chennai.
2. Department of Statistics, ICMR- National Institute for Research in Tuberculosis, Chennai.
3. Department of Clinical Research, ICMR- National Institute for Research in Tuberculosis, Chennai
4. Department of Pathology and Microbiology, ICMR-National Institute of Nutrition, Hyderabad.
5. Director In Charge, ICMR- National Institute for Research in Tuberculosis, Chennai, India.

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