Paraoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement

Circulation: Cardiovascular Genetics

Volumn 4, Issue 4, 2011, Pages 429-436

  Trenk, Dietmar ^a   Hochholzer, Willibald ^a   Fromm, Martin F ^b   Zolk, Oliver ^b   Valina, Christian M ^a   Stratz, Christian ^a   Neumann, Franz Josef ^a  

^a UNIVERSITY HEART CENTER FREIBURG BAD KROZINGEN   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Clopidogrel; Coronary artery disease; Coronary stent; Genetic polymorphisms; Platelets

Indexed keywords

ACETYLSALICYLIC ACID; ADENOSINE DIPHOSPHATE; ARYLDIALKYLPHOSPHATASE 1; CLOPIDOGREL; CYTOCHROME P450 2C19; MEMBRANE PROTEIN;

AGED; ALLELE; ARTICLE; CORONARY STENT; DEATH; ELECTIVE SURGERY; FEMALE; FLOW CYTOMETRY; GAIN OF FUNCTION MUTATION; GENETIC POLYMORPHISM; GENOTYPE; HEART INFARCTION; HUMAN; LOADING DRUG DOSE; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; MALE; MULTIVARIATE LOGISTIC REGRESSION ANALYSIS; NUCLEOTIDE SEQUENCE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROSPECTIVE STUDY; SINGLE NUCLEOTIDE POLYMORPHISM; STENT THROMBOSIS; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION;

ARYLDIALKYLPHOSPHATASE; GENOTYPE; HUMANS; MUTATION, MISSENSE; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PLATELET FUNCTION TESTS; POLYMORPHISM, SINGLE NUCLEOTIDE; STENTS; SURGICAL PROCEDURES, ELECTIVE; TICLOPIDINE;

EID: 80052790906     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.111.960112     Document Type: Article

References (34)

1. Kushner FG, Hand M, Smith SC Jr, King III SB, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DE Jr, Green LA, Hochman JS, Jacobs AK, Krumholz HM, Morrison DA, Ornato JP, Pearle DL, Peterson ED, Sloan MA, Whitlow PL, Williams DO. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54:2205-2241.
2. Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Sousa Uva M, Taggart D, Vahanian A, Auricchio A, Bax J, Ceconi C, Dean V, Filippatos G, Funck-Brentano C, Hobbs R, Kearney P, McDonagh T, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Vardas PE, Widimsky P, Alfieri O, Dunning J, Elia S, Kappetein P, Lockowandt U, Sarris G, Vouhe P, von Segesser L, Agewall S, Aladashvili A, Alexopoulos D, Antunes MJ, Atalar E, Brutel de la Riviere A, Doganov A, Eha J, Fajadet J, Ferreira R, Garot J, Halcox J, Hasin Y, Janssens S, Kervinen K, Laufer G, Legrand V, Nashef SA, Neumann FJ, Niemela K, Nihoyannopoulos P, Noc M, Piek JJ, Pirk J, Rozenman Y, Sabate M, Starc R, Thielmann M, Wheatley DJ, Windecker S, Zembala M. Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2010;31:2501-2555.
3. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107:2908-2913. (Pubitemid 36736631)
4. Müller I, Besta F, Schulz C, Massberg S, Schömig A, Gawaz M. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost. 2003;89:783-787. (Pubitemid 36603418)
5. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramirez C, Sabate M, Banuelos C, Hernandez-Antolin R, Escaned J, Moreno R, Alfonso F, Macaya C. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J. 2004;25:1903-1910. (Pubitemid 39452607)
6. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramirez C, Barrera-Ramirez C, Sabate M, Hernandez R, Moreno R, Escaned J, Alfonso F, Banuelos C, Costa MA, Bass TA, Macaya C. Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting. Thromb Res. 2005;115:101-108. (Pubitemid 39572762)
7. Gurbel PA, Bliden KP, Hayes KM, Yoho JA, Herzog WR, Tantry US. The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting. J Am Coll Cardiol. 2005;45:1392-1396. (Pubitemid 40615608)
8. Hochholzer W, Trenk D, Frundi D, Blanke P, Fischer B, Andris K, Bestehorn HP, Büttner HJ, Neumann FJ. Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention. Circulation. 2005;111:2560-2564. (Pubitemid 40740853)
9. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol. 2005;45:246-251. (Pubitemid 40094733)
10. Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, Gachet C, Montalescot G, Jennings LK, Kereiakes D, Sibbing D, Trenk D, Van Werkum JW, Paganelli F, Price MJ, Waksman R, Gurbel PA. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919-933.
11. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001;409:202-207. (Pubitemid 32144286)
12. Savi P, Labouret C, Delesque N, Guette F, Lupker J, Herbert JM. P2y(12), a new platelet ADP receptor, target of clopidogrel. Biochem Biophys Res Commun. 2001;283:379-383. (Pubitemid 32924702)
13. Kurihara A, Hagihara K, Kazui M, Ozeki T, Farid NA, Ikeda T. In vitro metabolism of antiplatelet agent clopidogrel: cytochrome P450 isoforms responsible for two oxidation steps involved in the active metabolite formation. Drug Metab Rev. 2005;37:99.
14. Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, Ikeda T, Kurihara A. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos. 2010;38:92-99.
15. Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006;108:2244-2247. (Pubitemid 44497506)
16. Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, Stratz C, Schmiebusch P, Bestehorn HP, Büttner HJ, Neumann FJ. Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol. 2008;51:1925-1934. (Pubitemid 351636443)
17. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849-857.
18. Hochholzer W, Trenk D, Fromm MF, Valina CM, Stratz C, Bestehorn HP, Büttner HJ, Neumann FJ. Impact of cytochrome P450 2C19 loss-offunction polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement. J Am Coll Cardiol. 2010;55:2427-2434.
19. Blatter MC, James RW, Messmer S, Barja F, Pometta D. Identification of a distinct human high-density lipoprotein subspecies defined by a lipoprotein-associated protein, K-45: identity of K-45 with paraoxonase. Eur J Biochem. 1993;211:871-879. (Pubitemid 23050064)
20. Bouman HJ, Schömig E, van Werkum JW, Velder J, Hackeng CM, Hirschhauser C, Waldmann C, Schmalz HG, ten Berg JM, Taubert D. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med. 2011;17:110-116.
21. Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, Bensimon G, Funck-Brentano C, Montalescot G. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009;373:309-317.
22. Giusti B, Gori AM, Marcucci R, Saracini C, Sestini I, Paniccia R, Buonamici P, Antoniucci D, Abbate R, Gensini GF. Relation of cytochrome P450 2C19 loss-of-function polymorphism to occurrence of drugeluting coronary stent thrombosis. Am J Cardiol. 2009;103:806-811.
23. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354-362.
24. Sibbing D, Stegherr J, Latz W, Koch W, Mehilli J, Dorrler K, Morath T, Schomig A, Kastrati A, von Beckerath N. Cytochrome P450 2C19 lossof-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J. 2009;30:916-922.
25. Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg PG, Ferrieres J, Danchin N, Becquemont L. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360:363-375.
26. Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot JS, Kastrati A, Montalescot G, Neumann FJ, Shen L, Sibbing D, Steg PG, Trenk D, Wiviott SD, Sabatine MS. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304:1821-1830.
27. Hochholzer W, Trenk D, Bestehorn HP, Fischer B, Valina CM, Ferenc M, Gick M, Caputo A, Büttner HJ, Neumann FJ. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol. 2006;48:1742-1750. (Pubitemid 44648629)
28. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36:959-969.
29. Hochholzer W, Trenk D, Frundi D, Neumann FJ. Whole blood aggregometry for evaluation of the antiplatelet effects of clopidogrel. Thromb Res. 2007;119:285-291. (Pubitemid 44918096)
30. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115:2344-2351. (Pubitemid 46685903)
31. Smolen A, Eckerson HW, Gan KN, Hailat N, La Du BN. Characteristics of the genetically determined allozymic forms of human serum paraoxonase/ arylesterase. Drug Metab Dispos. 1991;19:107-112.
32. Adkins S, Gan KN, Mody M, La Du BN. Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. Am J Hum Genet. 1993;52:598-608. (Pubitemid 23311330)
33. Billecke S, Draganov D, Counsell R, Stetson P, Watson C, Hsu C, La Du BN. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos. 2000;28: 1335-1342.
34. Helton TJ, Bavry AA, Kumbhani DJ, Duggal S, Roukoz H, Bhatt DL. Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: a meta-analysis of randomized trials. Am J Cardiovasc Drugs. 2007;7:289-297. (Pubitemid 47295838)