| Abstract |
Background: The CYP2C19 G681A (rs4244285) polymorphism, platelet indices, high platelet reactivity, and clopidogrel low-responsiveness have been shown to predict the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). However, the relationship between platelet indices and clopidogrel responsiveness is unclear.
Aims: To investigate the combined effect of CYP2C19 G681A polymorphism and platelet indices on clopidogrel responsiveness in Thai ACS subjects.
Methods: A total of 56 ACS subjects treated with clopidogrel were recruited. Polymorphism of CYP2C19 G681A was determined by polymerase chain reaction-restriction fragment length polymorphism techniques. Platelet reactivity in term of closure time (CT) was measured by using platelet function analyzer-200 (PFA-200). The CT ≤ 106 and exceeding 106 seconds were classified as clopidogrel low-responder and responder, respectively. Platelet indices were examined by automated analyzer XE-2100 (Sysmex, Japan).
Results: Individual with 681AA revealed significantly lower CT compared to 681GA and 681GG (p=0.002 and 0.001, respectively). However, no significant influence of the carrier of G681A on clopidogrel low-responder when compared to 681GG (p=0.051). Among platelet indices, only plateletcrit (PCT) revealed a significant increase in clopidogrel low-responder compared to clopidogrel responder group (p= 0.034). Based on ROC analysis, PCT at the cutoff point of 0.2 could predict clopidogrel low-responder with a sensitivity of 57.5% and a specificity of 66%. However, no significant influence of PCT ˃ 0.2 on clopidogrel low-responder when compared to PCT ≤ 0.2 (p=0.080). Interestingly, when combined 681GA or AA with PCT ˃ 0.2, the result revealed an increased risk of clopidogrel low-responsiveness compared to the group with 681GG + PCT ≤ 0.2 [OR (95% CI) = 4.3 (1.1, 16.5)].
Conclusion: These findings suggested that the combination of CYP2C19 G681A polymorphism with PCT enhance risk of clopidogrel low-responsiveness in Thai ACS subjects.
Key words: ACS; CYP2C19 G681A; Plateletcrit; Clopidogrel; Closure time
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Publication
Journal Publication
ไทย