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Background  Clopidogrel is a prodrug that undergoes in vivo bioactivation to show its antiplatelet effects. Recent studies have shown that cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogrel bioactivation. Here, we aim to determine the effects of genetic polymorphisms of  CYP  ( CYP  2C19*2,  CYP  2C19*3, and  CYP  2C19*17),  ABCB1  ( ABCB1  3435C>T,  ABCB1  129T>C, and  ABCB1  2677G>T/A), and  PON1  ( PON1  Q192R,  PON1  L55M, and  PON1  108C>T) on the development of stent thrombosis (ST) in patients receiving clopidogrel after percutaneous coronary intervention (PCI).    Methods and Results  We evaluated the incidence of ST (0.64%) in 4964 patients who were recruited in the CAPTAIN registry (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions). The presence of genetic polymorphisms was assessed in 20 subjects who developed ST after aspirin and clopidogrel therapy and in 40 age- and sex-matched control subjects who did not develop ST, which was documented after 9 months of angiographic follow-up. ST was acute in 5 subjects, subacute in 7, late in 7, and very late in 1. The presence of  CYP  2C19*2 allele was significantly associated with ST (adjusted odds ratio [ORadj]: 4.20, 95% confidence interval [CI], 1.263–9.544;  P  = 0.031). However, genetic variations in  PON1  and  ABCB1  showed no significant association with ST.    Conclusion  We conclude that in a Taiwanese population,  PON1  Q192R genotype is not associated with ST development after PCI. However, the presence of  CYP  2C19*2 allele is a risk factor for ST development after PCI.

Paraoxonase-1 Is Not a Major Determinant of Stent Thrombosis in a Taiwanese Population