Abstract

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 D 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 fasting 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) D 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.