Date of Award
Master of Science (MS)
Debra M. Moriarity
Devin M. Absher
Joseph D. Ng
Bioengineering., Blood lipids., Cardiovascular system--Diseases.
DNA methylation directly influences gene expression. Previous studies showed that diet and genetics influence blood lipid levels. However, the association between DNA methylation and lipid levels is unknown. This study demonstrates a link between epigenetic variation and fasting blood lipid levels, particularly in triglycerides and VLDL&minusC. Approximately 470,000 CpGs were evaluated in 995 individuals to find epigenome-wide associations between methylation and lipid levels. Two CpGs sites located within theCPT1A gene showed strong association with fasting triglyceride and VLDC&minusC levels. Furthermore there was an inverse relationship between methylation levels at the most significant CpG within CPT1Aand its fold expression levels. CPT1 initiates carnitine-dependent transport of long-chain fatty acids into the mitochondria, and its deficiency results in disabled beta-oxidation. This identifies a potential epigenetic mechanism converging on CPT1A through a powerful relationship between methylation signatures and fasting lipid levels. Future studies will identify potential treatment targets and biomarkers of cardiovascular disease.
Patel, Nikita, "The association of blood lipid levels with the epigenetic regulation of the CPT1A gene" (2013). Theses. 4.