Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI

• Published in: PloS one 2013-02, Vol.8 (2), p.e52779-e52779
• Main Authors: Park, Kyung Woo, Park, Jin Joo, Kang, Jeehoon, Jeon, Ki-Hyun, Kang, Si-Hyuck, Han, Jung-Kyu, Lee, Sang Eun, Yang, Han-Mo, Lee, Hae-Young, Kang, Hyun-Jae, Koo, Bon-Kwon, Oh, Byung-Hee, Park, Young-Bae, Kim, Hyo-Soo
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alleles; Aryldialkylphosphatase - genetics; Atherosclerosis; Biology; Blood platelets; Cardiovascular disease; Cholesterol; Clinical outcomes; Clopidogrel; Coronary artery; Coronary artery disease; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Coronary Artery Disease - surgery; Coronary vessels; Diabetes; Disease control; Drug delivery; Drug dosages; Enzymes; Female; Gene polymorphism; Genes; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genotype; Genotyping; Heart; Heart attack; Heart attacks; Heart diseases; High density lipoprotein; Humans; Implantation; Implants; Internal medicine; Lipids; Low density lipoprotein; Low density lipoproteins; Male; Medicine; Middle Aged; Myocardial infarction; Paraoxonase; Paraoxonase 1; Particle size; Patient outcomes; Patients; Percutaneous Coronary Intervention; Pharmacogenetics; Platelet Aggregation Inhibitors - therapeutic use; Platelets; Polymorphism; Polymorphism, Genetic; Prospective Studies; Risk analysis; Risk Factors; Stents; Surgical implants; Thromboembolism; Thrombosis; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052779

Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation. A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months. PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55-87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78-1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients. PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C.