Abstract
BackgroundSingle 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.MethodWe 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.ResultsProfound 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.ConclusionProfound 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0240-2) contains supplementary material, which is available to authorized users.
Highlights
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
None of the single nucleotide polymorphisms (SNPs) investigated associated with susceptibility to TB, either in main effects analysis, or in interaction with vitamin D status
Profound vitamin D deficiency was common among TB patients in this high-burden setting, and was independently associated with disease susceptibility
Summary
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. We conducted a case–control study to determine the influence of vitamin D status and single nucleotide polymorphisms (SNPs) in VDR, DBP and CYP2R1 on susceptibility to active TB in Pakistan, a high-burden setting where TB incidence in 2014 was estimated at 270 cases per 100,000 population per year [1]. Having demonstrated an independent association between vitamin D deficiency and susceptibility to active TB in the study population, we proceeded to investigate whether this was modified by SNPs in the vitamin D pathway
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