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Catechol-O-Methyltransferase and Cardiovascular Disease: MESA
Kathryn T Hall1, Elisabeth Battinelli2, Daniel I Chasman1
1Division of Preventive Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA.
Journal of the American Heart Association
|December 17, 2019
Summary
Genetic variations in catechol-O-methyltransferase (COMT) are linked to cardiovascular disease (CVD) risk. The COMT rs4818G allele was associated with lower CVD risk and fibrinogen levels in a multiethnic cohort.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Pharmacogenomics
Background:
- Genetic variations in catechol-O-methyltransferase (COMT), an enzyme crucial for estrogen and catecholamine metabolism, are implicated in cardiovascular disease (CVD).
- Previous studies suggested a potential role for COMT in thrombosis, particularly in relation to aspirin use.
- The COMT gene's influence on CVD risk warrants further investigation in diverse populations.
Purpose of the Study:
- To investigate the association between COMT gene variants (rs4818 and rs4680) and CVD risk.
- To explore the relationship between COMT variants and subclinical atherosclerosis measures like coronary artery calcium and carotid intima-media thickness.
- To examine whether COMT variants modify the preventive effects of aspirin on CVD.
Main Methods:
- Analysis of COMT variants rs4818 and rs4680 in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.
- Longitudinal follow-up for cardiovascular events over 65,957 person-years, with 498 events recorded.
- Assessment of associations with CVD risk, fibrinogen levels, coronary artery calcium, and carotid intima-media thickness.
Main Results:
- The COMT rs4818G allele was significantly associated with a reduced risk of CVD (HR, 0.85; 95% CI, 0.74-0.97; P=0.02), independent of traditional CVD risk factors.
- Fibrinogen levels were the only significantly associated risk factor with rs4818 (β, -3.65; SE, 1.35 mg/dL; P=0.007).
- No significant association was found between COMT variants and subclinical atherosclerosis measures (coronary artery calcium or carotid intima-media thickness).
Conclusions:
- The COMT rs4818G allele is associated with a lower risk of cardiovascular disease and reduced fibrinogen levels in a multiethnic population.
- These findings suggest that COMT may play a role in the later stages of cardiovascular disease development, potentially through mechanisms independent of early atherosclerosis.
- The study did not find evidence for COMT modifying the effect of aspirin on CVD prevention in this cohort.
Keywords:
aspirincardiovascular disease risk factorscatecholaminecatecholaminergic polymorphic ventricular tachycardiacatechol‐O‐methyltransferaseMore Related Videos
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