Associations of vitamin D binding protein variants with the vitamin D-induced increase in serum 25-hydroxyvitamin D

Background: Vitamin D deficiency is a global problem that may be improved by vitamin D supplementation; however, the individual's response to the intervention varies. We aimed to investigate possible genetic factors that may modify the impact of environmental exposure on vitamin D status. The candidate gene variant we investigated was the Gc gene-rs4588 polymorphism at the vitamin D receptor (DBP) locus. Methods: A total of 619 healthy adolescent Iranian girls received 50000 IU of vitamin D3 weekly for 9 weeks. Serum 25(OH) D concentrations, metabolic profiles and dietary intake were measured at baseline and after 9 weeks of supplementation. The genotypes of the DBP variant (rs4588) were analyzed using the TaqMan genotyping assay. Results: Our results revealed that the rs4588 polymorphism might be associated with serum 25-hydroxy vitamin D both at baseline (p value=0.03) and after intervention (p value=0.008). It seemed that the outcome of the intervention was gene-related so that the subjects with common AA genotype were a better responder to vitamin D supplementation (Changes (%) 469.5(427.1) in AA carriers vs. 335.8(530) in GG holders), and carriers of the less common GG genotype experienced a rise in blood glucose after 9 weeks (Changes (%) 0 (1.5)). Our findings also showed that the statistical interaction between this variant and supplementation was statistically significant (intervention effect p-value<0.001 and p-value SNP effect=0.03). The regression model also revealed that after adjusted for potential confounders, likelihood of affecting serum 25(OH)D in individuals who were homozygous for the uncommon allele G was less than those homozygous for the more common AA genotype (OR=4.407 (1.82-8.89); p=0.001). Conclusion: Serum vitamin 25(OH) D following vitamin 25(OH) D3 supplementation appears to be modified by genetic background. The Gc genetic variant, rs4588 encoding the vitamin D receptor seems to influence the response to vitamin D supplementation. Key words: Total 25(OH) D, Supplementation, Gc gene, rs4588

A genetic variant in the cytochrome P450 family 2 subfamily R member 1 determines response to vitamin D supplementation

Background Globally, about 1 billion people have inadequate levels of serum vitamin D and it is prevalent in all ethnicities and age groups. Few foods naturally contain sufficient vitamin D; therefore, most people get their requirements through supplementation. Hence vitamin D status is affected by genetic and environmental determinants including season of measurement, diet habitual, health status, body mass index and concurrent medication. Further studies are necessary to understand how genetic variation influences vitamin D metabolism. We aimed to explore the association between a potential vitamin D-related polymorphism (the rs10766197 polymorphism in the CYP2R1 gene) with the response to supplementation of vitamin D in 253 healthy Iranian girls. Material and method A total of 253 healthy subjects received 50,000 IU of vitamin D3 weekly for 9 weeks. Serum 25(OH)D concentrations and metabolic profiles were measured at baseline and after 9 weeks of supplementation. The genotypes of the CYP2R1 variant (rs10766197) were identified using TaqMan genotyping assays. Results Serum 25(OH)D during the supplementation, increased in all individuals. Subjects with a AA major genotype at this locus had higher vitamin D concentrations after intervention (Changes (%) 448.4% ± 425% in AA vs 382.7% ± 301% in GG). This genetic variant modulated the response to supplementation (p < 0.001 and p-value SNP = 0.05). Regression analysis showed that the probability of affecting serum 25(OH)D, in individuals who had homozygous major allele GG was two-fold higher than carriers of the uncommon allele A (OR = 2.1 (1–4.2); p = 0.03). Interestingly, the Hs-CRP was reduced in AA carries while was elevated in individuals with GG and AG genotypes, after high-dose vitamin D supplementation. Conclusion Changes in serum vitamin D and metabolic profile following high dose supplementation with vitamin D were associated with CYP2R1 polymorphism. Although carriers of the common G allele showed a greater response in the serum vitamin D