My dissertation focuses on associations of genetics, diet, and sunlight exposure on Vitamin D levels, and how these factors may alter response to certain medications. This study requires genotyping individuals for alleles important in vitamin D metabolism and correlating genotype with metabolic markers. These genes include the cytochrome P450 2R1 gene, which is important in activation of vitamin D. They also include the CYP3A genes, which dominate the absorption, distribution, metabolism, and elimination of a third of all drugs important in the treatment of disease. Variability in these genes can affect the efficacy and toxicity of a drug regimen, especially for drugs with a narrow therapeutic index. Expression of the CYP3A4 enzyme in the intestine increases as vitamin D levels increase, changing systemic exposure of an orally-administered drug. Thus, variability in vitamin D concentrations in the body may contribute to inter-individual differences in drug bioavailability and pharmacological responses.
Vitamin D is a fat-soluble vitamin found in the diet and synthesized in the skin from UVB exposure. It is important in controlling calcium levels, and low levels of its active metabolite have been associated with increased risk for a wide range of diseases, including rickets, depression, cancers, and diabetes. Its availability is altered by seasonal sun exposure, dietary intake, and genetic factors affecting the formation of active metabolites and their clearance.
Additionally, I am studying how ancestral language relationships can be used to describe the genetic clustering of individuals. Using language of ancestry can avoid some of the ethical issues presented by genetic testing for ancestry, and so could be a useful tool for improving genetic interpretation and benefit for all communities, with greater respect for community or individual privacy and values.