The relationship between clopidogrel resistance and CYPC19 gene polymorphism and serum leptin level

SUMMARYIntroduction: Platelet activation and aggregation play a crucial role after acute coronary syndrome and percutaneous coronary intervention. Clopidogrel is a thienopyridine derivative that inhibits platelet aggregation by blockade of platelet ADP P2Y12 receptor. Combination with aspirin for patients with acute coronary syndrome and percutaneous coronary intervention is accepted treatment approach. Inhibition of platelet aggregation by clopidogrel can vary between patients. Clopidogrel resistance can be described as the persistent activity of clopidogrel receptor despite an adequate antiplatelet regime. High platelet reactivity after clopidogrel was shown to be associated with adverse cardiovascular events, particularly stent thrombosis and cardiovascular death.Purpose: The aim of the study is to investigate relationship between clopidogrel resistance and obesity, serum leptin levels and CYP2C19 gene polymorphismMethods: In this study, 100 patients who have undergone percutaneous coronary intervention for coronary artery disease after their admission to hospital emergency department or cardiology clinic were included. Patients? demographic data, risk factors for cardiovascular disease, body mass index, use of drugs that can interact with clopidogrel, biochemical parameters, left ventricular functions, serum leptin levels and the presence of CYP2C19 * 2 and CYP2C19 * 3 mutant allele were compared between clopidogrel resistant and responsive groups. Clopidogrel platelet inhibition level is measured by the Verify Now © P2Y12 system. Patients whose PRU level > 240 were accepted resistant to clopidogrel, while PRU <240 ones were evaluated as responsive to clopidogrel. In addition, leptin levels > 15 ng / ml was considered to be hyperleptinemia.Results: In our study, relationship between the presence of CYP2C19 *2 and CYP2C19 *3 mutant alleles and clopidogrel resistance did not reach statistical significance. (p=0.073). The presence of CYP2C19 * 2 allele alone did not also achieve statistical significance. (p=0.141) Similarly, in terms of PRU value, patients carrying mutant alleles (CYP2C19* 12+22+13) PRU were 260.88±70.97, while patients carrying normal alleles PRU were 213.69±70.99 (p=0.093). Leptin levels were respectively 8.03 ± 7.27 and 5.82 ± 5:48, in clopidogrel resistant and responsive groups. However, this difference did not reach statistical significance. ( p= 0.116). Clopidogrel resistance is significantly more in patients with leptin level > 15. (p= 0.017) PRU value was higher in in patients with leptin level > 15, statistically significant relationship was found. (292.18±70.11 vs 208.76±66.98, p= 0.001). Similarly, in patients with BMI> 30, statistically significant greater number of clopidogrel resistance was observed. ( p=0.015 )Conclusion: Clopidogrel resistance is seen more in obese, hyperleptinemic patients. Increasing the dose of clopidogrel should be considered in this group. For the relationship between clopidogrel resistance and CYP2C19 gene polymorphism, more patients carrying mutant alleles and new studies are needed