INVESTIGATING THE GENETIC AND NON-GENETIC FACTORS UNDERLYING POPULATION DIFFERENCES IN IRON STATUS AND ABSORPTION
Access to this document is restricted. Some items have been embargoed at the request of the author, but will be made publicly available after the "No Access Until" date.
During the embargo period, you may request access to the item by clicking the link to the restricted file(s) and completing the request form. If we have contact information for a Cornell author, we will contact the author and request permission to provide access. If we do not have contact information for a Cornell author, or the author denies or does not respond to our inquiry, we will not be able to provide access. For more information, review our policies for restricted content.
Humans have no regulated mechanisms for excreting excess iron (Fe). Thus, dietary Fe absorption must be tightly controlled to ensure optimal body Fe levels. Failure to regulate Fe absorption in response to daily Fe demands can lead to Fe deficiency or Fe overload, with both states being equally detrimental to health. Altogether, my doctoral research aims to improve our understanding of Fe homeostasis and its implications for human health by exploring both ends of Fe’s dual nature across three main projects. The Fe Genes in East Asians (EA) and Northern Europeans (NE) Study (FeGenes; Project 1) aims to understand biochemical, hormonal and genetic factors underlying differences in Fe homeostasis between healthy young adults of EA and NE descent. My dissertation begins with a comprehensive literature review in Chapter 1, setting the groundwork for FeGenes. Subsequent chapters delve into specific aspects of Fe homeostasis within the FeGenes population: Chapter 2 examines the Fe status, Chapter 3 investigates the Fe regulatory hormones, and Chapter 4 delves into Fe absorption. Although not formally incorporated into the dissertation, ongoing research is underway to uncover genetic factors responsible for the observed ancestry-driven variations in Fe accumulation. Building upon the FeGenes study, I obtained funding through an American Heart Association (AHA) pre-doctoral fellowship to explore the clinical implications of excessive Fe accumulation (Project 2). Chapter 5 of my dissertation employs a Mendelian randomization approach to elucidate the relationship between Fe status and cardiovascular disease. Additionally, I conducted an analysis of lipid biomarkers within the FeGenes cohort, which will contribute to a future manuscript. Pregnancy is one of the most dynamic life stages in which Fe needs increase drastically to support the maternal-fetal-placental unit. To explore determinants of placental Fe regulation and trafficking, I undertook an additional project (Project 3) capitalizing on an existing placental archive from pregnant populations at greater risk for Fe deficiency. In Chapter 6, I characterize placental Fe content (Chapter 6A), placental expression of the main Fe trafficking proteins (Chapter 6B), and placental expression of Fe regulatory hormones (Chapter 6C) and evaluate these in relation to placental, maternal and neonatal Fe-related factors.