The Multi-Ethnic Investigation of Gene and Gene-Environment Interactions for Biochemical Markers associated with Cardiovascular Disease Public Deposited

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  • March 22, 2019
Creator
  • Ellis, Jaclyn Willette
    • Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
Abstract
  • Cardiovascular disease (CVD) is the leading cause of illness and death worldwide with an estimated annual one million deaths occurring in the United States alone. Biomarkers of systemic inflammation, such as C-reactive protein (CRP), and metabolism, such as homocysteine, have been shown to be predictive of clinical CVD. CRP, an acute phase inflammatory protein, has been shown to have a moderate degree of heritability with estimates ranging between 25% and 40%. Previous reports have identified approximately twenty genetic loci to be associated with CRP. Homocysteine is a sulfur-containing nonessential amino acid derived from methionine and recently, evidence has elucidated a relationship between this amino acid and inflammation. Similar to CRP, elevated levels of homocysteine have been linked to cardiovascular complications, and heritability estimates are in the range of 47% to 70%. Further, while it has been well-demonstrated that environmental influences such as cigarette smoking significantly contribute to the development of CVD, it is less clear how genetic variants modify the effects of these risk factors on cardiovascular biomarkers. There are only few studies that have assessed gene-environment interaction effects on CVD-related biomarkers. Finally, most genetic studies of CVD-related biomarkers have focused on populations of non-European ancestry. Therefore, we assessed how common and less common gene variants influence CRP and homocysteine levels in a multi-ethnic setting, and investigated whether genetic variants in two glutathione-S-transferase genes, which play a detoxification role, modify the association between cigarette smoking and CRP level. We used African-American (AA), European-American (EA), and European (EU) participants from several cohort studies from the Candidate gene and Association Resource (CARe), the Women's Health Initiative (WHI), and Cooperative Health Research in the Region Augsburg (KORA) studies. We identified novel genetic risk factors for CRP and homocysteine levels as well as evidence for the interplay between genes and environment on CRP. Overall, our results provide important insight regarding the pathophysiology of CVD and atherosclerosis as well as place emphasis on the need to conduct more genome-wide and candidate gene association studies in non-European populations.
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  • In Copyright
Advisor
  • Lange, Leslie
Degree
  • Doctor of Philosophy
Graduation year
  • 2013
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