Paraoxonase-1 is not a major determinant of stent thrombosis in a Taiwanese population.
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).


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.


CONCLUSIONS
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.
Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Dong-Yi
DY
Chen
Chao-Yung
CY
Wang
Ming-Shien
MS
Wen
Tsong-Hai
TH
Lee
Yen
Y
Chu
Ming-Jer
MJ
Hsieh
Shang-Hung
SH
Chang
Cheng-Hung
CH
Lee
Jian-Liang
JL
Wang
Chun-Chi
CC
Chen
Laing-Suei
LS
Lu
Ming-Ta
MT
Lee
San-Jou
SJ
Yeh
Fun-Chiung
FC
Lin
I-Chang
IC
Hsieh
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People; D003328:Coronary Thrombosis / Q000453:epidemiology / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D012042:Registries; D012307:Risk Factors; D015607:Stents / Q000009:adverse effects*; D013624:Taiwan / Q000453:epidemiology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase