Genetic Polymorphisms of CYP۲C۱۹ and Resistance to Clopidogrel Therapy among Iranian Patients Suffering from Ischemic Heart Disease

Background: Clopidogrel is a standout amongst the most ordinarily recommended medications to avoid ischemic occasions taking after coronary disorder or stant position. However, impaired responses the therapy as well as resistance to the therapy have also been reported. Genetic variants play an important role in clopidogrel biotransformation of its active metabolite that may subsequently influence the antiplatelet effect of clopidogrel. The objective of this study was to evaluate the prevalence of the cytochrome P۴۵۰ (CYP۴۵۰) ۲C۱۹ enzyme (CYP۲C۱۹) genotypes which are involved in the activation of clopidogrel in a random Iranian population of various ethnic groups (Persian, Azari, Kurd, etc.). Molecular analysis of CYP۲C۱۹ polymorphisms may be helpful in the determination of optimal antiplatelet therapy. Materials and Methods: CYP۲C۱۹ (*۱/*۲/*۳) variants were assessed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR–RFLP) assays in a representative sample of ۱۵۴ Iranian patients with ischemic heart disease. Results: The frequencies of CYP۲C۱۹ *۱ (normal genotype), *۲ (heterozygote) and *۳ (homozygote) were ۱۱۲ (۷۲.۷%), ۳۶ (۲۳.۴%) and ۶ (۳.۹%), respectively. Conclusion: The United States Food and Drug Administration (FDA) recommendations are more useful to be practiced in our country compared with other countries. Physicians should identify poor metabolizers for consideration of other antiplatelet medications or alternative dosing strategies.

Keywords:

Clopidogrel , ischemic heart disease , CYP۲C۱۹ polymorphisms , PCR–RFLP