Mehrane Mehramiz1, Sayyed Saeid Khayyatzadeh2, Habibollah Esmaily3, Faezeh Ghasemi4, Kiana Sadeghi-Ardekani4, Maryam Tayefi4, Seyed Jamal Mirmousavi5, Parichehr Hanachi6, H Bahrami-Taghanaki7, Saeed Eslami8, Hasan Vatanparast9, Gordon A Ferns10, Majid Ghayour-Mobarhan11, Amir Avan12. 1. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Nutrition and Food Security Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Social Determinants of Health Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran. 4. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Community Medicine, Community Medicine Department, Medical School, Sabzevar University of Medical Sciences, Sabzevar, Iran. 6. Department of Biology, Biochemistry Unit, Al Zahra University, Tehran, IR Iran. 7. Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. 8. Chinese and Complementary Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 9. College of Pharmacy and Nutrition, University of Saskatchewan, Health Sciences E-Wing, Saskatoon, Saskatchewan, Canada. 10. Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK. 11. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ghayourm@mums.ac.ir. 12. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: avana@mums.ac.ir.
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 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 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) 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.
RCT Entities:
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 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) 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.