ABSTRACT
BACKGROUND: Canadian First Nation populations have experienced endemic and epidemic tuberculosis (TB) for decades. Vitamin D-mediated induction of the host defence peptide LL-37 is known to enhance control of pathogens such as Mycobacterium tuberculosis. OBJECTIVE: Evaluate associations between serum levels of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation participants (N = 34) and assess correlations with single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). DESIGN: Venous blood was collected from all participants at baseline (winter and summer) and in conjunction with taking vitamin D supplements (1,000 IU/day) (winter and summer). Samples were analysed using ELISA for concentrations of vitamin D and LL-37, and SNPs in the VDR and VDBP regions were genotyped. RESULTS: Circulating levels of 25(OH)D were not altered by vitamin D supplementation, but LL-37 levels were significantly decreased. VDBP and VDR SNPs did not correlate with serum concentrations of 25(OH)D, but LL-37 levels significantly decreased in individuals with VDBP D432E T/G and T/T, and with VDR SNP Bsm1 T/T genotypes. CONCLUSIONS: Our findings suggest that vitamin D supplementation may not be beneficial as an intervention to boost innate immune resistance to M. tuberculosis in the Dene population.
Subject(s)
Antimicrobial Cationic Peptides/genetics , Endemic Diseases , Receptors, Calcitriol/genetics , Tuberculosis/epidemiology , Vitamin D-Binding Protein/genetics , Vitamin D/analogs & derivatives , Adult , Canada/epidemiology , Cohort Studies , Female , Genetic Markers , Humans , Incidence , Male , Middle Aged , Polymorphism, Single Nucleotide , Population Groups , Prospective Studies , Risk Assessment , Tuberculosis/blood , Tuberculosis/drug therapy , Tuberculosis/genetics , Vitamin D/administration & dosage , Vitamin D/blood , CathelicidinsABSTRACT
The wide spectrum of vitamin D activity has focused attention on its potential role in the elevated burden of disease in a northern Canadian First Nations (Dené) cohort. Vitamin D insufficiency, and gene polymorphisms in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) have been implicated in susceptibility to infectious and chronic diseases. The objectives of this study were to determine the contribution of vitamin D from food, and measure the serum concentrations of 25-hydroxyvitamin D(3) (25-OHD(3)) and VDBP in Dené participants. Single nucleotide polymorphisms (SNPs) associated with the dysregulation of the innate immune response were typed and counted. Potential correlations between the SNPs and serum concentrations of 25-OHD(3) and VDBP were evaluated. Venous blood was collected in summer and winter over a one-year period and analyzed for 25-OHD(3) and VDBP concentrations (Nâ=â46). A questionnaire was administered to determine the amount of dietary vitamin D consumed. Sixty-one percent and 30% of the participants had 25-OHD(3) serum concentrations <75 nmol/L in the winter and summer respectively. Mean vitamin D binding protein concentrations were within the normal range in the winter but below normal in the summer. VDBP and VDR gene polymorphisms affect the bioavailability and regulation of 25-OHD(3). The Dené had a high frequency of the VDBP D432E-G allele (71%) and the Gc1 genotype (90%), associated with high concentrations of VDBP and a high binding affinity to 25-OHD(3). The Dené had a high frequency of VDR Fok1-f allele (82%), which has been associated with a down-regulated Th1 immune response. VDBP and VDR polymorphisms, and low winter 25-OHD(3) serum concentrations may be risk factors for infectious diseases and chronic conditions related to the dysregulation of the vitamin D pathway.
