Association between Vitamin D Deficiency and Single Nucleotide Polymorphisms in the Vitamin D Receptor and GC Genes and Analysis of Their Distribution in Mexican Postmenopausal Women

Abstract

Genome-wide association studies in people with European ancestry suggest that polymorphisms in genes involved in vitamin D (VD) metabolism have an effect on serum concentrations of 25-hydroxyvitamin D. However, nothing is known about these polymorphisms in populations with Amerindian ancestry. Our aim was to evaluate the association between genetic variants on the vitamin D receptor (VDR) and the vitamin D binding protein (GC) genes, involved in the VD pathway, and VD deficiency in 689 unrelated Mexican postmenopausal women. We also described the frequencies of these variants in 355 postmenopausal women from different ethnic groups. Based on our preliminary results of 400 unrelated Mexican postmenopausal women, three single nucleotide polymorphisms (SNPs) were selected for genotyping. The SNPs rs4516035 in VDR and rs2282679 in GC were associated with VD deficiency. Additionally, women who carried three risk alleles had a 3.67 times higher risk of suffering VD deficiency, compared to women with no risk alleles (p = 0.002). The rs4516035-C allele frequency in the Amerindian population was enriched in the South East region of Mexico. In contrast, the highest frequency of the rs2298850-C allele, a proxy for the tag SNP rs2282679, was observed in the South region. Our results indicate that genetic variants in VDR and GC genes are associated with VD deficiency in Mexican postmenopausal women. Moreover, an association was observed for the variants rs3794060 and rs4944957 of the DHCR7/NADSYN1 gene with osteopenia/osteoporosis.

Serum Proteomic Analysis Reveals Vitamin D-Binding Protein (VDBP) as a Potential Biomarker for Low Bone Mineral Density in Mexican Postmenopausal Women

“…On the other hand, experimental evidence has shown that some of these SNPs can influence VDBP serum levels [44,45]. Based on this, altered serum VDPB levels observed in postmenopausal women with low BMD could be influenced by these polymorphisms [46]. Additional studies are needed to evaluate the association between variants in the GC gene, serum VDBP levels, and BMD variation.…”

Serum Retinol but Not 25(OH)D Status Is Associated With Serum Hepcidin Levels in Older Mexican Adults

“…Some polymorphism associated with biomarkers of inflammation, as well as those for the VD pathway, may better reflect the risk rather than serum baseline levels, since the prevalence of these polymorphs may vary across different ethnicities and populations [51]. The polymorphism associated with VDR in the Mexican population is higher in the southern region of Mexico (30%), being present in the 29% of Mayan ethnic population [52]. This risk profile may explain, that even in normal 1,25(OH2)D3 and 25(OH)D serum concentration, VD is not properly used by the cell to execute their multiple action.…”

The Role of Polymorphisms in Vitamin D-Related Genes in Response to Vitamin D Supplementation

“…When selecting SNPs (single-nucleotide polymorphisms), we aimed at choosing the ones previously reported to be associated with vitamin D-related traits in addition to a few SNPs we wanted to explore [5]. These SNPs were selected from genes associated with vitamin D and included cytochrome P450 family 2, R (CYP2R1) [5,[22][23][24][25][26][27], cytochrome P450 family 24 subfamily A member 1 (CYP24A1) [22,[27][28][29][30][31], the 1-alpha-hydroxylase (CYP27B1) [32][33][34][35], the 7-dehydrocholesterol reductase/NAD synthetase 1 (DHCR7/NADSYN1) [26,36], the vitamin D receptor (VDR) [37,38], and the vitamin D-binding protein GC (group-specific component) [20][21][22]26,28,39,40].…”