title: Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants.
abstract: There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti-platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti-aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non-significant.
authors: Cardiology Department, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain.
authors: Efrén
authors: E
authors: Martínez-Quintana
authors: José M
authors: JM
authors: Medina-Gil
authors: Fayna
authors: F
authors: Rodríguez-González
authors: Paloma
authors: P
authors: Garay-Sánchez
authors: José M
authors: JM
authors: Limiñana
authors: Pedro
authors: P
authors: Saavedra
authors: Antonio
authors: A
authors: Tugores
mesh_terms: D000368:Aged; D000483:Alleles; D000787:Angina Pectoris / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D015331:Cohort Studies; D003327:Coronary Disease / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D065689:Cytochrome P-450 CYP2C19 Inhibitors / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage; D012008:Recurrence; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D065689:Cytochrome P-450 CYP2C19 Inhibitors; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine; D001241:Aspirin
keywords: CYP2C19; aspirin; clopidogrel; omeprazole; paraoxonase