Abstract

It is possible that vitamin D acts as a neurosteroid and that vitamin D deficiency may have an adverse impact on brain function and cognitive function. There are a few reports that have demonstrated an association between polymorphisms of genes involved in vitamin D metabolism and neurodegenerative disease. We aimed to evaluate the relationship between common, functional vitamin D-associated gene variants and cognitive abilities and to investigate the effect size of this polymorphism on cognitive capabilities associated with high-dose vitamin D supplementation. A total of 319 healthy adolescents received a high dose of vitamin D (50,000 IU)/week for 9 weeks. A questionnaire was used to assess cognitive abilities at baseline and after treatment. The genotypes of the CYP2R1-rs10766197 and GC-rs4588 variants were determined using TaqMan genotyping techniques. At baseline, total cognitive ability scores were higher in the AA group who were homozygous for the uncommon allele, compared with the other (AG and GG) genotypes of the CYP2R1-rs10766197 polymorphism (104.9 +/- 27.8 vs. 79.1 +/- 38.8 vs. 73.1 +/- 25.6; p < 0.001, respectively). During the supplementation period, cognitive ability scores increased in individuals with the AG and GG genotypes, while individuals with a AA genotype did not show significant change in total score after intervention (p = 0.17). For GC SNP (rs4588), no major differences at baseline and trial-net change of cognitive tasks score were observed between the genotypes under three genetic models (p(SNP) = 0.67). Vitamin D supplements have trait-dependent effects on cognitive performance that suggests a causal role for vitamin D in cognitive performance. The rs10766197 variant, near the CYP2R1 gene locus, significantly modified the efficacy of high-dose vitamin D3 supplementation for its effects on improving cognitive abilities indicate that some subjects might require a higher dose to benefit from in terms of cognitive performance.