The influence of renal function on the association of rs854560 polymorphism of paraoxonase 1 gene with long-term prognosis in patients after myocardial infarction

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.

The rs2228145 polymorphism in the interleukin-6 receptor and its association with long-term prognosis after myocardial infarction in a pilot study

“…As described previously [18–20], the registry included consecutive patients with STEMI admitted to our department in the years 2001–2005 and treated invasively within 12 h from symptoms onset. On the day of admission, after obtaining informed written consent, blood samples were collected.…”

The Association of Paraoxonase-1 Polymorphism with Carotid Artery Stenosis among Elderly Chinese Population

“…The rs662 SNP leads to transition between adenine and guanine nucleobases that results in glutamineto-arginine substitution at codon 192 (Q192R) [12]. The genotype AA is linked with an unfavorable lipid status and low PON1 activity in patients [13]. However, the associations of PON1 polymorphism with CAS risk remain unknown.…”

The Relation between eNOS −786 C/T, 4 a/b, MMP-13 rs640198 G/T, Eotaxin 426 C/T, −384 A/G, and 67 G/A Polymorphisms and Long-Term Outcome in Patients with Coronary Artery Disease

“…Some of the polymorphisms did not show any significant association with the prognosis of CAD or the results were controversial. On the other hand, several papers reported promising results; for example, genome-wide association study (GWAS) identified polymorphisms in loci 1p13.3 (rs599839), 1q41 (rs17465637), and 3q22.3 (rs9818870) [ 7 ], or the variants of paraoxonase 1 gene (rs854560) [ 5 ] and phospholipase A2 gene (rs1805017) [ 6 ]. These data were repetitively confirmed by following studies [ 8 – 14 ].…”