RETRACTED ARTICLE: Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis
This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04–1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03–1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05–1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08–1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01–3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09–4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.
KeywordsPON1 Antiplatelet treatment Percutaneous coronary intervention Meta-analysis
We would like to acknowledge the reviewers for their helpful comments on this paper. This work was supported by Natural Science Foundation of China (NSFC) (grant #81202598), Shanghai Municipal Public Health Bureau (grant #2009068).
Conflict of interest
The authors declare no conflict of interest.
- 1.Caggegi A, Capodanno D, Capranzano P, Chisari A, Ministeri M, Mangiameli A, Ronsivalle G, Ricca G et al (2011) Comparison of one-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients with unprotected left main coronary artery disease and acute coronary syndromes (from the customize registry). Am J Cardiol 108:355–359. doi: 10.1016/j.amjcard.2011.03.050 CrossRefPubMedGoogle Scholar
- 2.Mause SF, Ritzel E, Liehn EA, Hristov M, Bidzhekov K, Muller-Newen G, Soehnlein O, Weber C (2010) Platelet microparticles enhance the vasoregenerative potential of angiogenic early outgrowth cells after vascular injury. Circulation 122:495–506. doi: 10.1161/CIRCULATIONAHA.109.909473 CrossRefPubMedGoogle Scholar
- 4.Chhatriwalla AK, Bhatt DL (2008) Should dual antiplatelet therapy after drug-eluting stents be continued for more than one-year? Dual antiplatelet therapy after drug-eluting stents should be continued for more than one-year and preferably indefinitely. Circ Cardiovasc Interv 1:217–225. doi: 10.1161/CIRCINTERVENTIONS.108.811380 CrossRefPubMedGoogle Scholar
- 6.Park KW, Park JJ, Kang J, Jeon KH, Kang SH, Han JK, Lee SE, Yang HM et al (2013) Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI. PLoS One 8:e52779. doi: 10.1371/journal.pone.0052779 PubMedCentralCrossRefPubMedGoogle Scholar
- 7.Trenk D, Hochholzer W, Fromm MF, Zolk O, Valina CM, Stratz C, Neumann FJ (2011) Paraoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement. Circ Cardiovasc Genet 4:429–436. doi: 10.1161/CIRCGENETICS.111.960112 CrossRefPubMedGoogle Scholar
- 9.Hulot JS, Collet JP, Cayla G, Silvain J, Allanic F, Bellemain-Appaix A, Scott SA, Montalescot G (2011) CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv 4:422–428. doi: 10.1161/CIRCINTERVENTIONS.111.963025 CrossRefPubMedGoogle Scholar
- 10.Wang X, Fan Z, Huang J, Su S, Yu Q, Zhao J, Hui R, Yao Z et al (2003) Extensive association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol 23:328–334. doi: 10.1161/01.ATV.0000051702.38086.C1 CrossRefPubMedGoogle Scholar
- 16.Price MJ, Murray SS, Angiolillo DJ, Lillie E, Smith EN, Tisch RL, Schork NJ, Teirstein PS et al (2012) Influence of genetic polymorphisms on the effect of high- and standard-dose clopidogrel after percutaneous coronary intervention: the gift (genotype information and functional testing) study. J Am Coll Cardiol 59:1928–1937. doi: 10.1016/j.jacc.2011.11.068 CrossRefPubMedGoogle Scholar
- 21.Campo G, Ferraresi P, Marchesini J, Bernardi F, Valgimigli M (2011) Relationship between paraoxonase q192r gene polymorphism and on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention. J Thromb Haemost 9:2106–2108. doi: 10.1111/j.1538-7836.2011.04457.x CrossRefPubMedGoogle Scholar
- 22.Sibbing D, Koch W, Massberg S, Byrne RA, Mehilli J, Schulz S, Mayer K, Bernlochner I et al (2011) No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J 32:1605–1613. doi: 10.1093/eurheartj/ehr155 CrossRefPubMedGoogle Scholar
- 23.Tang XF, Wang J, Zhang JH, Meng XM, Xu B, Qiao SB, Wu YJ, Chen J et al (2013) Effect of the CYP2C19 2 and 3 genotypes, abcb1 C3435T and pon1 Q192R alleles on the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people after percutaneous coronary intervention. Eur J Clin Pharmacol 69:1103–1112. doi: 10.1007/s00228-012-1446-8 CrossRefPubMedGoogle Scholar
- 24.Verschuren JJ, Boden H, Wessels JA, van der Hoeven BL, Trompet S, Heijmans BT, Putter H, Guchelaar HJ et al (2013) Value of platelet pharmacogenetics in common clinical practice of patients with st-segment elevation myocardial infarction. Int J Cardiol 167:2882–2888. doi: 10.1016/j.ijcard.2012.07.020 CrossRefPubMedGoogle Scholar
- 27.Simon T, Steg PG, Becquemont L, Verstuyft C, Kotti S, Schiele F, Ferrari E, Drouet E et al (2011) Effect of paraoxonase-1 polymorphism on clinical outcomes in patients treated with clopidogrel after an acute myocardial infarction. Clin Pharmacol Ther 90:561–567. doi: 10.1038/clpt.2011.193 CrossRefPubMedGoogle Scholar