Vitamin D: Genetics and Genomic Effects

Abstract

Vitamin D is normally thought of as an environmental factor. However, even when all the factors known to in fl uence vitamin D concentrations, as measured by 25-OH vitamin D (25(OH)D), are taken into account, there is substantial interindividual variability in vitamin D levels. While it is possible that other, unde fi ned, environmental factors contribute to the large interindividual variability noted with 25(OH)D levels, perhaps a more likely explanation for these differences lies in genetics. Indeed, recent studies have demonstrated that 25(OH)D levels are heritable and strongly in fl uenced by variants in key vitamin D regulatory genes. In this chapter, we will review the evidence that supports circulating vitamin D levels as being heritable, discuss the candidate gene studies demonstrating an association of vitamin D pathway genes with 25(OH)D levels, detail the genome-wide association studies (GWAS) performed to date, and relate the signi fi cance of data generated via ChIP-Seq methods to interindividual variation in response to vitamin D. Following this overview of the genetic determinants of vitamin D level/activity, we will review the salient studies relating genetic variation within the vitamin D pathway to speci fi c respiratory disease outcomes. While these latter studies are in their relative infancy, they re fl ect the potential for vitamin D, in combination with genetic variation, to influence pulmonary disease susceptibility and therapy.