title: Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.
authors: Kyung Woo
authors: KW
authors: Park
authors: Jin Joo
authors: JJ
authors: Park
authors: Jeehoon
authors: J
authors: Kang
authors: Ki-Hyun
authors: KH
authors: Jeon
authors: Si-Hyuck
authors: SH
authors: Kang
authors: Jung-Kyu
authors: JK
authors: Han
authors: Sang Eun
authors: SE
authors: Lee
authors: Han-Mo
authors: HM
authors: Yang
authors: Hae-Young
authors: HY
authors: Lee
authors: Hyun-Jae
authors: HJ
authors: Kang
authors: Bon-Kwon
authors: BK
authors: Koo
authors: Byung-Hee
authors: BH
authors: Oh
authors: Young-Bae
authors: YB
authors: Park
authors: Hyo-Soo
authors: HS
authors: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000235:genetics*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D043303:Aryldialkylphosphatase; D013988:Ticlopidine