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BMC pulmonary medicine
May 10, 2016;16 (1): 73.

Vitamin D deficiency associates with susceptibility to tuberculosis in Pakistan, but polymorphisms in VDR, DBP and CYP2R1 do not.

Kashaf Junaid, Abdul Rehman, David A Jolliffe, Tahir Saeed, Kristie Wood, Adrian R Martineau
Author Information
  1. Kashaf Junaid: Department of Microbiology and Molecular Genetics, University of the Punjab, Quaid-e-Azam Campus, Lahore, 5400, Pakistan. kashaf_junaid@hotmail.com.
  2. Abdul Rehman: Department of Microbiology and Molecular Genetics, University of the Punjab, Quaid-e-Azam Campus, Lahore, 5400, Pakistan.
  3. David A Jolliffe: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AB, UK.
  4. Tahir Saeed: Gulab Devi Chest Hospital, Lahore, Pakistan.
  5. Kristie Wood: Genome Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
  6. Adrian R Martineau: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AB, UK.
PMID: 27160686 DOI: 10.1186/s12890-016-0240-2

Abstract

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and the vitamin D binding protein (DBP) have been reported to modify the influence of vitamin D deficiency on susceptibility to active tuberculosis (TB) in the UK, but this phenomenon has not been investigated in settings with a high TB burden. SNPs in CYP2R1, which encodes a vitamin D 25-hydroxylase enzyme, are known to influence vitamin D status, but their potential role in determining susceptibility to TB has not previously been investigated in any setting.
METHOD: We conducted a case-control study in 260 pulmonary TB patients and 112 controls recruited in Lahore, Pakistan. Analyses were conducted to test for main effects of vitamin D status and SNPs in VDR (rs731236, rs2228570 and rs1544410), DBP (rs7041 and rs4588) and CYP2R1 (rs2060793, rs10500804 and rs10766197) on susceptibility to TB, and to investigate whether these SNPs modify the association between vitamin D status and disease susceptibility.
RESULTS: Profound vitamin D deficiency (serum 25-hydroxyvitamin D concentration ≤ 20 nmol/L) was common among TB patients (118/260, 45 %), and was independently associated with susceptibility to TB (adjusted odds ratio 1.87, 95 % CI 1.15 to 3.04, P = 0.01). However, none of the SNPs investigated associated with susceptibility to TB, either in main effects analysis, or in interaction with vitamin D status.
CONCLUSION: Profound vitamin D deficiency was common among TB patients in this high-burden setting, and was independently associated with disease susceptibility. However, no statistically significant associations between SNPs in the vitamin D pathway and disease susceptibility was demonstrated.

Keywords

Hypovitaminosis D Tuberculosis Vitamin D Vitamin D 25-hydroxylase Vitamin D Receptor Vitamin D binding protein

References

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MeSH Term

Adolescent
Adult
Case-Control Studies
Cholestanetriol 26-Monooxygenase
Cytochrome P450 Family 2
DNA-Binding Proteins
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Pakistan
Polymorphism, Single Nucleotide
Receptors, Calcitriol
Signal Transduction
Transcription Factors
Tuberculosis, Pulmonary
Vitamin D
Vitamin D Deficiency
Young Adult

Chemicals

DBP protein, human
DNA-Binding Proteins
Receptors, Calcitriol
Transcription Factors
VDR protein, human
Vitamin D
25-hydroxyvitamin D
Cytochrome P450 Family 2
CYP2R1 protein, human
Cholestanetriol 26-Monooxygenase
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0DvitaminsusceptibilityTBSNPsVitamindeficiencystatusVDRDBPinvestigatedCYP2R1patientsdiseaseassociatedpolymorphismsbindingproteinmodifyinfluencetuberculosis25-hydroxylasesettingconductedPakistanmaineffectsProfoundcommonamongindependently1HoweverBACKGROUND:SinglenucleotidegenesencodingreceptorreportedactiveUKphenomenonsettingshighburdenencodesenzymeknownpotentialroledeterminingpreviouslyMETHOD:case-controlstudy260pulmonary112controlsrecruitedLahoreAnalysestestrs731236rs2228570rs1544410rs7041rs4588rs2060793rs10500804rs10766197investigatewhetherassociationRESULTS:serum25-hydroxyvitaminconcentration ≤ 20 nmol/L118/26045 %adjustedoddsratio8795 %CI15304P = 001noneeitheranalysisinteractionCONCLUSION:high-burdenstatisticallysignificantassociationspathwaydemonstratedassociatesnotHypovitaminosisTuberculosisReceptor

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