Vitamin D in a Northern Canadian First Nation Population: Dietary Intake, Serum Concentrations and Functional Gene Polymorphisms

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.

Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility

“…The longer form exhibits 1.7x less efficiency than the shorter form (33). Furthermore, high frequency of the VDR (ATG) (f) allele was associated with a decrease in Th1 immune response (17). A previous study on the role of the FokI SNP demonstrated the presence of increased vitamin D levels in carriers of the TT (ff) genotype, as compared with carriers of the CC (FF) genotype (34).…”

“…A previous study demonstrated that GC single nucleotide polymorphisms (SNP) may affect blood plasma vitamin D levels (17). The VDR gene also exists in certain genetic variants, which may modulate the biological effect of vitamin D in target cells (18).…”

Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers of BRCA1/BRCA2 mutations

“…To date, certain polymorphisms situated in GC have been reported to be associated with vitamin D metabolite levels in blood plasma (13,52). The GC rs7041 SNP was associated with high concentrations of VDBP in blood plasma and a high binding affinity to 25(OH)D 3 in a Canadian cohort (13).…”

“…Furthermore, Luo et al (49) demonstrated that the BsmI SNP was responsible for the significantly lowered VDR mRNA levels in patients bearing the A (B) allele as compared to bearers of the GG (bb) genotype. The FokI polymorphism results in the creation of two protein variants; longer VDR, encoded by the changed allele form (ATG) (f), has an additional three amino acids and is 1.7 times less efficient than the shorter, common allele form (ACG) (F) (50 (13) demonstrated high frequency of VDR f allele associated with a downregulation of the Th1 immune response.…”

“…VDR forms heterodimers with RXR and binds to DNA to initiate a series of epigenetic events leading to chromatin rebuilding and initiation of transcription (11,12). Evidence has indicated that a GC single-nucleotide polymorphism (SNP) is associated with blood plasma vitamin D levels (13). Furthermore, the VDR gene also contains various SNPs, a number of which may alter 1,25(OH) 2 D 3 action (8).…”