Genetic Variation in Cytochrome P450 2R1 and Vitamin D Binding Protein Genes are associated with Vitamin D Deficiency in Adolescents.

ABSTRACT

Background: Genome Wide Association Studies (GWAS) have evaluated several genes related to vitamin D synthesis, metabolism and transport. They have proposed a genetic basis for low levels of vitamin D in the blood. The current study aims to investigate the relationship between certain vitamin D-associated gene variants and vitamin D deficiency in Iranian adolescents. Methods: In this case-control study, the genomic DNA was extracted by Real Time PCR High Resolution Melt (HRM). All measurements were carried out with triple repetition. The following factors were assessed single nucleotide polymorphisms (SNPs) in Vitamin D binding protein (DBP, rs2282679), 7-Dehydrocholesterol reductase (DHCR7, rs12785878) and Cytochrome P450 2R1 (CYP2R1, rs10741657). Results: the genomic DNA of blood samples obtained from 481 adolescents. Participants with hypovitaminosis D were compared with a control group. The average vitamin D level of sufficient subjects (controls) was 44.88±14.01 ng/mL, while subjects who were insufficient (cases) had an average vitamin D level of 7.03±1.24 ng/mL. No statistically significant differences were found in the allelic and genotypic distributions between genders. The SNP frequency in CYP2R1 (rs10741657) and DBP (rs2282679) in the vitamin D deficient group was significantly higher than in the control group (p-values < 0.001 and 0.01 respectively). There were no statistically significant differences in the DHCR7 SNP (rs12785878) distributions between the Vitamin D deficient group and control group. Conclusion: The present study demonstrated evidence of the ability of the SNPs under investigation to predict circulating vitamin D concentration. Further study is needed to better understand if and how genetic factors contribute to vitamin D levels, and certain skeletal-associated disorders in adolescents.