Objectives: To assess the impact of different CYP2C19*2 polymorphisms on clinical outcomes and the effects of CYP2C19*2 polymorphism on predicting clinical outcomes in association with classic risk factors in patients with acute coronary syndromes (ACS). Methods: Between July 2008 and September 2009, 497 consecutive patients with ACS who were admitted to the West China Hospital of Sichuan University were enrolled and underwent CYP2C19*2 determination. The clinical outcomes were the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. Results: Baseline characteristics were balanced between noncarrier, heterozygous and homozygous groups of the CYP2C19*2 variant. The clinical endpoint occurred more frequently in the homozygous group (HR 4.86, CI 1.62–14.56, p = 0.005). After multivariable analysis, the CYP2C19*2 genetic variant was an independent predictor of cardiovascular events (HR 5.96, CI 1.77–20.03, p = 0.0039) as well as GRACE score and Killip class. The combination of CYP2C19*2 with GRACE score and Killip class increases the potential to predict adverse outcomes. Conclusions: Homozygosity (A/A) for CYP2C19*2 mutant is an independent determinant of prognosis in patients with ACS. The combination of CYP2C19*2 polymorphism with classic risk factors may be a useful tool to predict the risk of cardiovascular events.

Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE, Chavey WE, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS: ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction. J Am Coll Cardiol 2007;50:1–157.
Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, Akkerhuis KM, Harrington RA, Deckers JW, Armstrong PW, Lincoff AM, Califf RM, Topol EJ, Simoons ML: Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. Circulation 2000;101:2557–2567.
Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA: Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 2003;163:2345–2353.
Yan AT, Yan RT, Huynh T, Casanova A, Raimondo FE, Fitchett DH, Langer A, Goodman SG: Understanding physicians’ risk stratification of acute coronary syndromes: insights from the Canadian ACS 2 Registry. Arch Intern Med 2009;169:372–378.
Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Werf FV, Goodman SG, Granger CB, Steg PG, Gore JM, Budaj A, Avezum A, Flather MD, Fox KAA: A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 2004;291:2727–2733.
Khot UN, Jia G, Moliterno DJ, Lincoff AM, Khot MB, Harrington RA, Topol EJ: Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification. JAMA 2003:290;2174–2181.
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.
Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P: Cytochrome P450 2C19 loss-offunction polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 2006;108:2244–2247.
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.
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. The Lancet 2009;373:309–317.
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.
Rosemary J, Adithan C: The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance. Curr Clin Pharmacol 2007;2:93–109.
Xie HG, Stein CM, Kim RB, Wilkinson GR, Flockhart DA, Wood AJ: Allelic, genotypic and phenotypic distributions of S-mephenytoin 4’-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world. Pharmacogenetics 1999;9:539–549.
Xie HG: Genetic variations of S-mephenytoin 4’-hydroxylase (CYP2C19) in the Chinese population. Life Sci 2000;66:175–181.
Jose R, Chandrasekaran A, Sam SS, Gerard N, Chanolean S, Abraham BK, Satyanarayanamoorthy K, Peter A, Rajagopal K: CYP2C9 and CYP2C19 genetic polymorphisms: frequencies in the south Indian population. Fundam Clin Pharmacol 2005;19:101–105.
Xie HG, Kim RB, Stein CM, Wilkinson GR, Wood AJ: Genetic polymorphism of (S)-mephenytoin 4’-hydroxylation in populations of African descent. Br J Clin Pharmacol 1999;48:402–408.
Yin OQ, Tomlinson B, Chow AH, Waye MM, Chow MS: Omeprazole as a CYP2C19 marker in Chinese subjects: assessment of its gene-dose effect and intrasubject variability. J Clin Pharmacol 2004;44:582–589.
Yan AT, Yan RT, Tan M, Casanova A, Labinaz M, Sridhar K, Fitchett DH, Langer A, Goodman SG: Risk scores for risk stratification in acute coronary syndromes: useful but simpler is not necessarily better. Eur Heart J 2007;28:1072–1078.
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