Abstract
Paraoxonase 1 (PON1) is an enzyme responsible for the antioxidant properties of high density lipoprotein (HDL). The activity of PON1 is decreased in patients with coronary artery disease, myocardial infarction or chronic kidney disease. rs662 and rs854560 are single nucleotide polymorphisms (SNPs) associated with PON1 activity and 10-year cardiovascular mortality of patients with stable coronary artery disease. We investigated the association of rs662 and rs854560 SNPs of the PON1 gene with 5-year mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively. We analyzed the data of consecutive patients with STEMI treated with primary PCI. Genotyping was performed with the TaqMan method. The analyzed end-point was total 5-year mortality. Additional subgroup analysis was performed for survival of patients depending on their eGFR. The study group comprised 634 patients (mean age 62.3 ± 11.85 years; 25.2 % of women, n = 160; PCI successful in 92.3 %, n = 585). No clinically relevant differences in baseline characteristics were found between the genotypes. No association between either genotype and 5-year mortality was found: p = 0.4 for the rs662 SNP, p = 0.73 for the rs854560 one (log-rank test). However, in a subgroup of patients with eGFR below median value (78.6 ml/min/1.73m2) the rs854560 AA homozygotes had a significantly lower probability of survival (p = 0.047, log-rank test). The AA genotype of the rs854560 SNPs of the PON1 gene is associated with increased mortality in patients after myocardial infarction in the subpopulation of patients with lowered eGFR. This phenomenon may be explained by potentially lower PON1 activity in kidney disease.
Highlights
Paraoxonase 1 (PON1) is an enzyme associated with high density lipoprotein (HDL) that is responsible for its antioxidant properties
The activity of PON1 was shown to be decreased in patients with coronary artery disease, myocardial infarction or chronic kidney disease [2,3,4,5]
In patients with coronary artery disease decreased PON1 activity leads to malfunction of the HDL molecule with subsequent activation of the LOX-1 receptor and endothelial PKCβII, followed by inhibition of eNOS-activating pathways and decreased NO production [6]
Summary
Paraoxonase 1 (PON1) is an enzyme associated with high density lipoprotein (HDL) that is responsible for its antioxidant properties. The activity of PON1 was shown to be decreased in patients with coronary artery disease, myocardial infarction or chronic kidney disease [2,3,4,5]. In patients with coronary artery disease decreased PON1 activity leads to malfunction of the HDL molecule with subsequent activation of the LOX-1 receptor (an endothelial lectin-like oxidized LDL-receptor) and endothelial PKCβII, followed by inhibition of eNOS-activating pathways and decreased NO production [6]. In this way, the dysfunctional HDL of impaired function fails to stimulate endothelial repair. The rs662 SNP leads to transition between adenine and guanine nucleobases that results in
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