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Published on: September 22, 2020
AMPD1 (C34T) polymorphism and clinical outcomes in patients undergoing myocardial revascularization
Maria Grazia Andreassi1, Nicoletta Botto, Franco Laghi-Pasini
1Institute of Clinical Physiology, Pisa, Italy. andreas@ifc.cnr.it
Insights
The adenosine monophosphate deaminase 1 (AMPD1) gene C34T variant did not improve outcomes after coronary revascularization. This suggests alternative cardioprotective mechanisms may be involved in AMPD1 gene function.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Pharmacogenomics
Background:
- The adenosine monophosphate deaminase 1 (AMPD1) gene C34T variant is linked to better survival in heart failure and coronary artery disease.
- This association is hypothetically related to increased adenosine production.
Purpose of the Study:
- To investigate if the AMPD1 (-) allele is associated with improved prognosis after coronary revascularization.
- To assess the relationship between AMPD1 polymorphism and plasma adenosine levels.
Main Methods:
- 161 patients undergoing coronary revascularization (PTCA or CABG) were studied.
- A composite endpoint of adverse cardiac events was tracked.
- Plasma adenosine levels were measured in a subset of patients using HPLC.
Main Results:
- No significant difference in the composite endpoint was observed between AMPD1 (-) allele carriers and non-carriers (9.8% vs. 11.5%).
- Low ejection fraction (<40%) was the only independent predictor of adverse events.
- Plasma adenosine levels were similar in both AMPD1 (-) and AMPD1 (+) allele groups.
Conclusions:
- The AMPD1 (-) allele is not associated with a better outcome after coronary revascularization.
- Alternative cardioprotective pathways related to AMPD1 gene function, possibly involving long-term adenosine production, may explain observed survival benefits.
Background:
C34T variant of adenosine monophosphate deaminase 1 (AMPD1) gene has been associated with a prolonged survival in heart failure and coronary artery disease, hypothetically linked to an enhanced production of adenosine.
Design:
Since adenosine administration is a promising approach for the prevention of the ischemia-reperfusion in myocardial revascularization, the aim of this study was to investigate whether the AMPD1 (-) allele is associated with a favorable prognosis after coronary revascularization. In addition, we assessed the association between AMPD1 polymorphism and plasma adenosine levels.
Methods:
We investigated a total of 161 patients receiving coronary revascularization (70 percutaneous transluminal coronary angioplasty and 91 coronary artery bypass graft). They were investigated for a composite endpoint including recurrent angina, non-fatal MI, target vessel revascularization, heart failure and cardiac death. Plasma adenosine was also measured by high-performance liquid chromatography methods on a subset of 25 patients.
Results:
During the follow-up period (7.0+/-0.3 months), the overall combined endpoint accounted for 17 events (10 cardiac-related deaths, 6 revascularization procedures and 1 congestive heart failure). The composite endpoint was 9.8% for AMPD1 (-) allele carriers vs. 11.5% for non-carriers (log-rank statistic, p=n.s.). In the logistic analysis only low (
Conclusions:
Our results indicate that AMPD1 (-) allele is not associated with a more favorable outcome after coronary revascularization. Alternative cardioprotective pathways of the AMPD1 gene-involving an enhanced chronic long-term production of adenosine-might be responsible for survival.
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