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Prognostic value of paraoxonase 1 in patients undergoing coronary artery bypass grafting surgery
Anna Wysocka1, Marek Cybulski2, Henryk Berbeć2
1Department of Cardiology, Medical University of Lublin, Lublin, Poland.
Insights
Paraoxonase 1 (PON1) gene polymorphism and plasma activity are linked to coronary heart disease (CHD) risk after coronary artery bypass grafting (CABG). Lower PON1 activity and TT genotype increase adverse cardiac events and reduce event-free survival.
Area of Science:
- Cardiovascular Genetics
- Biochemistry
- Surgical Outcomes
Background:
- Coronary artery bypass grafting (CABG) is a major intervention for coronary heart disease (CHD).
- Identifying genetic and enzymatic risk factors for adverse cardiac events post-CABG is crucial for patient management.
- The paraoxonase 1 (PON1) gene and its enzyme activity are implicated in cardiovascular health.
Purpose of the Study:
- To investigate the association between the -108C/T polymorphism of the PON1 gene and plasma PON1 enzyme activity.
- To determine if these factors predict adverse cardiac events following CABG surgery.
Main Methods:
- Seventy-one patients undergoing CABG for CHD were studied.
- Genomic DNA was extracted for PON1 gene polymorphism analysis.
- PON1 enzyme activity was measured using paraoxon and phenyl acetate substrates.
Main Results:
- Significant differences in PON1 activity were observed across PON1 genotypes (CC, CT, TT).
- Lower plasma PON1 activity (<193.5 U/ml) was associated with a higher risk of serious cardiac events (p=0.03).
- The TT genotype correlated with shorter event-free survival compared to CT and CC genotypes (p=0.009).
Conclusions:
- PON1 gene polymorphism and plasma enzyme activity are associated with CHD occurrence and prognosis after CABG.
- High PON1 activity, particularly with CC and CT genotypes, appears to reduce symptom recurrence and improve outcomes post-CABG.
- These findings highlight PON1 as a potential biomarker for cardiovascular risk stratification in CABG patients.
Background:
The aim of this study was to evaluate whether -108C/T polymorphism of the paraoxonase 1 (PON1) gene and the plasma enzyme activity are risk factors for adverse cardiac events after coronary artery bypass grafting (CABG).
Material And Methods:
Seventy-one patients with coronary heart disease (CHD) undergoing CABG were enrolled in the study. Genomic DNA was extracted from the venous blood using the Gen Elute™ Blood Genomic DNA kit (Sigma) according to the manufacturer's instructions. PON1 activity was measured in 50 mM glycine/NaOH buffer (pH 10.5) containing 1.0 mM paraoxon, and 1.0mM CaCl2.
Results:
The mean PON1 activity toward paraoxon and toward phenyl acetate was equal (166.5 ± 86.9 U/ml and 96.0 ± 47.2 U/ml, respectively) in patients with CHD. The -108C/T polymorphism of PON1 gene was tested. In CABG patients, PON1 activities in dependence on genotypes were significantly different and equalled 266.2 ± 117.9 U/ml for CC, 178.8 ± 64.7 U/ml for CT, and 98.9 ± 59.2 U/ml for TT genotype. Patients with PON1 activity lower than 193.5 U/ml exhibited significantly increased risk of a serious cardiac event in comparison with patients with PON1 activity higher or equal to this value (p=0.03). Additionally, TT genotype was significantly associated with shorter time of event-free survival in comparison with CT and CC genotypes (p=0.009).
Conclusions:
The PON1 polymorphism and enzyme plasma activity are associated with CHD occurrence. High PON1 activity connected with the presence of CC and CT genotypes decreases the recurrence of symptoms of coronary heart disease and improve prognosis after CABG.
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