Abstract
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 D3 (25-OHD3) 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-OHD3 and VDBP were evaluated. Venous blood was collected in summer and winter over a one-year period and analyzed for 25-OHD3 and VDBP concentrations (N = 46). A questionnaire was administered to determine the amount of dietary vitamin D consumed. Sixty-one percent and 30% of the participants had 25-OHD3 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-OHD3. 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-OHD3. 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-OHD3 serum concentrations may be risk factors for infectious diseases and chronic conditions related to the dysregulation of the vitamin D pathway.
Highlights
Vitamin D has a wide spectrum of activity including calcium and bone homeostasis, cardiovascular and immune system function, as well as skin, muscle and cell proliferation
The purpose of this study was to; 1) determine the contribution of vitamin D from food sources and measure the serum concentrations of 25-OHD3 and vitamin D binding protein (VDBP); 2) detect the frequency of vitamin D receptor (VDR) and VDBP Single nucleotide polymorphisms (SNPs) that are associated with dysregulation of the innate immune response, and 3) evaluate potential correlations between VDBP SNPs and VDBP serum concentrations
There were no significant correlations between age, gender or body mass index (BMI) in either season
Summary
Vitamin D has a wide spectrum of activity including calcium and bone homeostasis, cardiovascular and immune system function, as well as skin, muscle and cell proliferation. The elevated burden of both infectious and non-infectious diseases borne by Canada’s Aboriginal (First Nations, Metis and Inuit) people has focused attention on the potential causal, preventive and/or therapeutic role, if any, of this vitamin [1]. Case reports of rickets, elevated fracture risk and low bone mineral density in First Nations and Inuit children and women suggest that vitamin D deficiency is not rare in these groups [2,3,4]. In addition to the classical function of vitamin D on skeletal development, 1,25(OH)2D3 binds with VDRs found in many tissue types to regulate cell growth and maturation, stimulate insulin secretion, and modulate the function of activated T- and B-lymphocytes and macrophages [5]
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