The PON1 Q192R variant was not associated with post-clopidogrel platelet aggregation or cardiovascular events (HR 0.46; 95% CI 0.20-1.06; P=0.07).
Cohort (n=793)
Does the PON1 Q192R gene variant determine clopidogrel response (platelet aggregation) and cardiovascular events in patients receiving clopidogrel?
The PON1 Q192R gene variant is not associated with clopidogrel response or cardiovascular events, challenging previous reports that suggested it was a major determinant of clopidogrel efficacy.
Hazard Ratio: 0.46 (95% CI 0.2–1.06)
p-value: p=0.07
A common functional variant in paraoxonase 1 (PON1), Q192R, was recently reported to be a major determinant of clopidogrel response. This variant was genotyped in 566 participants of the Amish Pharmacogenomics of Anti-Platelet Intervention (PAPI) study and in 227 percutaneous coronary intervention (PCI) patients. Serum paraoxonase activity was measured in a subset of 79 PAPI participants. PON1 Q192R was not associated with pre- or post-clopidogrel platelet aggregation in the PAPI study (P = 0.16 and P = 0.21, respectively) or the PCI cohort (P = 0.47 and P = 0.91, respectively). The Q192 allele was not associated with cardiovascular events (hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.20-1.06; P = 0.07). No correlation was observed between paraoxonase activity and post-clopidogrel platelet aggregation (r(2) < 0.01, P = 0.78). None of 49 additional PON1 variants evaluated was associated with post-clopidogrel platelet aggregation. These findings do not support a role for PON1 as a determinant of clopidogrel response.
Lewis et al. (Wed,) conducted a cohort in Clopidogrel response (n=793). PON1 Q192R variant was evaluated on Cardiovascular events (HR 0.46, 95% CI 0.20-1.06, p=0.07). The PON1 Q192R variant was not associated with post-clopidogrel platelet aggregation or cardiovascular events (HR 0.46; 95% CI 0.20-1.06; P=0.07).
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