Paraoxonase-1 Q192R polymorphism is not associated with clopidogrel response in Chinese stroke patients.
It is well known that CYP2C19*2/*2 is associated with attenuated response to clopidogrel, but recent findings indicated that in white patients, paraoxonase-1 (PON1) 192Q/Q was a major determinant of clopidogrel efficacy. The objective of this research was to assess the impact of PON1 Q192R polymorphism on the maximum platelet aggregation (MPA) and the anti-platelet effect of clopidogrel in clopidogrel-treated Chinese stroke patients. The study recruited 183 eligible Chinese stroke patients treated with a loading dose of 300-mg clopidogrel and a 75-mg daily maintenance dose. CYP2C19*2 and PON1 Q192R were genotyped, a subcohort of 13 patients with CYP2C19 *2/*2 genotype was excluded. Finally 170 patients with CYP2C19*1/*1 (wild-type homozygotes, n = 87) or CYP2C19*1/*2 (mutant heterozygotes, n = 83) were enrolled in the study population. These patients were divided into three groups according to their PON1 Q192R genotype: wild-type homozygotes, PON1 192QQ, n = 17; mutant heterozygotes, PON1 192QR, n = 81; mutant homozygotes, PON1 192RR, n = 72. MPA was measured by light transmittance aggregometry (LTA) to assess platelet function after seven 75-mg maintenance doses of clopidogrel before discharge. In those patients who were carriers of 1 mutant allele (PON1 Q/R192), ADP-induced MPA were not significantly different compared with wild-type homozygous patients [30.5% (IQR, 17.5 to 49.1%) versus 25.0% (IQR, 10.0 to 52.5%), respectively; P = 0.910]. In addition, in the patients who were carriers of the 2 mutant allele (PON1 R/R192), MPA were also not significantly different from wild-type homozygous patients [29.2% (IQR, 15.0 to 43.4%) versus 25.0% (IQR, 10.0 to 52.5%), respectively; P = 0.717]. Results of a multivariable linear regression model demonstrated that PON1 192R allele carriage was not independently associated with ADP-induced MPA measurements (P = 0.408). PON1 Q192R polymorphism does not seem to exhibit any impact on MPA and clopidogrel response at all.
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Jie
J
Yang
Jun-Shan
JS
Zhou
Jie
J
Tan
Bang-Shun
BS
He
Jian-Jun
JJ
Zou
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People; D000077144:Clopidogrel; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D020521:Stroke / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D043303:Aryldialkylphosphatase; D013988:Ticlopidine