COMMON GENETIC VARIANTS IN CHOLINE, FOLATE, AND VITAMIN D METABOLIC PATHWAYS INFLUENCE METABOLISM IN WOMEN OF REPRODUCTIVE AGE MEETING NUTRIENT INTAKE RECOMMENDATIONS

Abstract

Nutrient needs are a population-wide distribution, and can vary dramatically from person to person. Factors known to influence individual nutrient needs include common genetic polymorphisms as well as pregnancy and lactation, physiological states that are generally associated with an increased nutrient requirement. This doctoral dissertation examines the effects of common genetic variants in choline, folate, and vitamin D metabolic pathways on metabolism at recommended nutrient intakes. Interactions between genetic and reproductive factors that influence metabolism were also examined. While the genetic variants examined herein have been studied in conditions of nutrient deprivation or among non-pregnant women, these studies extend prior work to conditions of nutrient adequacy that are relevant to the population at large and to include pregnancy and lactating individuals, who have an increased risk for nutrient inadequacy, and much to gain from adequacy. We identified that common genetic variants impairing folate enzymes increase the metabolic use of choline for phosphatidylcholine production. In addition, variants in choline metabolizing enzymes altered choline dynamics and partitioning. Lastly, vitamin D binding protein rs7041 genotype altered vitamin D metabolism in pregnant women. Comprehensively, these findings provide evidence for differences in metabolism and nutrient needs at recommended intakes, and suggest personalized recommendations may be necessary to achieve optimal health and nutrition.