Genomics of Vitamin D Supplementation and Warfighter Nutritional Resilience
Name: Mary McCarthy
Organization: The Geneva Foundation
Performance Site: Madigan Army Medical Center, Fort Lewis, WA
Year Published: 2015
The increasing awareness of vitamin D deficiency as a public health epidemic, and the knowledge gap regarding the clinical and physiologic relevance of this, warrant scientific investigation to better understand skeletal and non-skeletal effects of this ubiquitous steroid hormone. A genomics-based approach will target identified candidate genes and search for variants that may explain the response observed in biomarkers and symptoms when deficient individuals are repleted. The long-term objective of this study is to translate findings from next-generation sequencing (NGS) technology into clinically meaningful data regarding vitamin D supplementation for Service Members (SM) who may be at risk for musculoskeletal disorders and immune dysfunction that impacts physical performance and military readiness. We propose the following specific aims: 1) explore the phenotypic expression of vitamin D status in a cohort of SM to determine common symptoms associated with deficiency/insufficiency states; 2) examine the effect of vitamin D levels on broad gene expression from carefully chosen candidate genes known to influence vitamin D status, bone density, and immune function; and 3) evaluate changes in gene expression levels between and within groups supplemented with low vs high vitamin D, and compare to healthy controls. This prospective, randomized, double-blind trial will enroll 105 SM in the Northwest to evaluate frequency, symptoms, and genomic expression of vitamin D levels using survey instruments, immunologic and bone biomarkers, and NGS of white blood cells pre- and post-supplementation with oral vitamin D over 3 months. Participant follow-up at 12 months will evaluate maintenance of adequate circulating vitamin D; this timeframe represents a typical deployment period. Representation from Army, Navy, and Air Force SM of both genders and diverse ethnicity is highly desirable. Factors known to be associated with deficiency states such as sun exposure, diet, family history, and body mass index will be recorded and examined for impact on treatment response. A bioinformaticist will interpret gene expression data and a biostatistician will employ techniques for dimension reduction of these data and cluster analysis while applying a correction factor for multiple testing.
This proposal focuses on the imperatives voiced by nurse leaders who challenge nurse scientists to validate threats to public health using genomic data to build an evidence base for disease prevention. This innovative research will advance military nursing science and narrow the knowledge gap regarding the molecular basis for physiological responses regulated by vitamin D impacting nutritional resilience and overall health.