Epidemiological, pharmacogenomic and clinical impact of catechol-O-methyltransferase on cardiovascular disease

Information

  • Research Project
  • 10438085
  • ApplicationId
    10438085
  • Core Project Number
    K01HL130625
  • Full Project Number
    3K01HL130625-05S1
  • Serial Number
    130625
  • FOA Number
    PA-20-272
  • Sub Project Id
  • Project Start Date
    2/1/2016 - 9 years ago
  • Project End Date
    1/9/2022 - 3 years ago
  • Program Officer Name
    SCOTT, JANE
  • Budget Start Date
    9/10/2021 - 4 years ago
  • Budget End Date
    1/9/2022 - 3 years ago
  • Fiscal Year
    2021
  • Support Year
    05
  • Suffix
    S1
  • Award Notice Date
    9/9/2021 - 4 years ago

Epidemiological, pharmacogenomic and clinical impact of catechol-O-methyltransferase on cardiovascular disease

PROJECT SUMMARY / ABSTRACT Extension of the funding for this K01 award will support completion of a critical career development goal of a junior investigator in cardiovascular epidemiology and pharmacogenomics, with special emphasis on the role of catechol-O-methyltransferase (COMT) in cardiovascular disease (CVD) and preventive treatment. The extension is warranted because of delays resultING from the COVID-19 pandemic. Despite significant strides in prevention and management, CVD remains a leading cause of death in the United States. Pharmacogenomics, the study of how an individual?s genome affects their treatment response, has expanded our understanding of the pathophysiology and treatment of CVD. However, gene-drug interactions have been difficult to assess in epidemiologic and clinical studies, in part because of the large sample sizes required for genome-wide association studies of these interactions and lack of strong candidate genes. COMT, which encodes a key enzyme in degradation of catecholamines including epinephrine, norepinephrine and catechol estrogen, is a strong candidate gene with plausible physiological links to both CVD and drug metabolism. Through this K01 we demonstrated COMT genetic effects on CVD risk with aspirin and estrogen replacement in the Multiethnic Study of Atherosclerosis, supporting our earlier findings in the Women?s Health Study. Given the widespread use of aspirin for prevention of CVD, it is imperative that we understand the generalizability, mechanism and impact of the COMT locus itself and drugs that may share common molecular pathways and networks with it. This translational research proposal addresses these gaps by conducting a clinical trial to examine effects of native aspirin on platelet function as a function of COMT genotype. As an emerging genetic locus with pleiotropic CVD and drug interaction effects, COMT is an excellent model system to probe the multiple molecular pathways and networks involved in cardiovascular function, disease and treatment and thus guide the development of novel strategies to attenuate CVD risk, and a promising example in which to develop personal expertise in cardiovascular epidemiology, systems biology, clinical trials, and other key career development milestones.

IC Name
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
  • Activity
    K01
  • Administering IC
    HL
  • Application Type
    3
  • Direct Cost Amount
    47736
  • Indirect Cost Amount
    3819
  • Total Cost
    51555
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    837
  • Ed Inst. Type
  • Funding ICs
    NHLBI:51555\
  • Funding Mechanism
    OTHER RESEARCH-RELATED
  • Study Section
  • Study Section Name
  • Organization Name
    BRIGHAM AND WOMEN'S HOSPITAL
  • Organization Department
  • Organization DUNS
    030811269
  • Organization City
    BOSTON
  • Organization State
    MA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    021156110
  • Organization District
    UNITED STATES