ADAMTS-13 activity and ischemic heart disease: a Mendelian randomization study
C M Schooling1,2, S Luo2, G Johnson1
1Graduate School of Public Health and Health Policy, City University of New York, New York, NY, USA.
Journal of Thrombosis and Haemostasis : JTH
|August 13, 2018
Summary
Genetically predicted ADAMTS-13 activity was inversely associated with ischemic heart disease (IHD). This suggests that targeting ADAMTS-13 activity could offer new therapeutic strategies for preventing and treating IHD.
Area of Science:
- Genetics and Cardiovascular Medicine
- Biochemistry and Molecular Biology
Background:
- Cardiovascular disease is the leading global cause of mortality, with limited new pharmaceutical treatments.
- ADAMTS-13, known for its role in clotting disorders, shows an inverse association with ischemic heart disease (IHD) in observational studies.
- Emerging risk factors and the need for novel therapeutic targets highlight the importance of investigating proteins like ADAMTS-13.
Purpose of the Study:
- To determine the unconfounded effect of ADAMTS-13 activity on ischemic heart disease (IHD) using Mendelian randomization.
- To investigate the relationship between ADAMTS-13 and diabetes and lipid profiles.
- To provide genetic validation for ADAMTS-13 as a potential therapeutic target for IHD.
Main Methods:
- Utilized Mendelian randomization with genetic variants strongly associated with ADAMTS-13 activity.
- Applied inverse variance weighted (IVW) analysis to large case-control studies of IHD and diabetes, and a lipid study.
- Assessed sensitivity using weighted median and MR-Egger regression methods.
Main Results:
- Genetically predicted ADAMTS-13 activity showed a consistent inverse association with IHD (OR 0.91; 95% CI 0.86-0.97).
- No significant association was found between genetically predicted ADAMTS-13 activity and diabetes or HDL/LDL cholesterol levels.
- ADAMTS-13 antigen levels, based on genetic variants, were not associated with any of the studied outcomes.
Conclusions:
- This study provides genetic evidence supporting ADAMTS-13 activity as a valid target for intervention in ischemic heart disease.
- Repurposing existing therapeutics that increase ADAMTS-13 activity or developing new interventions could offer novel prevention and treatment strategies for IHD.
- Further research into environmental or dietary factors influencing ADAMTS-13 activity may also yield benefits for cardiovascular health.
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