Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical Outcomes

Abstract

Vitamin D status is defined by the circulating concentration of 25-hydroxyvitamin D.1,2 In large, prospective cohort studies, lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of hip fracture, myocardial infarction (MI), cancer, and death.3-10 In experimental models, disruption of the vitamin D–endocrine axis stimulates inflammatory cytokines, activates the renin-angiotensin system, and impairs skeletal mineralization.11-13 The totality of these findings suggests that low 25-hydroxyvitamin D concentration may be a modifiable risk factor for many chronic diseases, which has motivated ongoing clinical trials to test whether vitamin D supplementation can reduce the risk of disease development.14 Laboratory testing for serum 25-hydroxyvitamin D and empirical therapy with vitamin D supplements have increased dramatically worldwide, with substantial associated costs.