European Journal of Molecular & Clinical Medicine

Recently, the prevalence of unstable variants of angina pectoris (NVS) among men at a young age has increased markedly. A significant role in the inflammation of the atherosclerotic plaque, which underlies the pathogenesis of NVS, is assigned to cytokines by the mediator. To date, the role of cytokine gene polymorphism in the development of NVS associated with inflammatory processes has been proven.

According to the World Health Organization (WHO), cardiovascular disease (CVD) is the leading cause of death and disability in countries around the world, with ST segment elevated myocardial infarction (STEMI) leading the way. Despite advances such as the widespread introduction of many effective drugs, angioplasty and surgical treatments into clinical practice, CVD kills 17.3 million people annually, accounting for 30% of all deaths worldwide. This figure is projected to increase to 23.6 million by 2030. In the world, including in Uzbekistan, over the past two decades there has been an increase in morbidity and mortality from cardiovascular pathology.

background: coronary artery disease is the leading cause of death in developing countries and the main treatment strategy includes pci which is usually followed by dual antiplatelet therapy (dapt) with aspirin and clopidogrel. Clopidogrel resistance from genetic polymorphisms incyp2c19 gene involved in hepatic activation of clopidogrel leads to clopidogrel nonresponsiveness and may result in increased adverse clinical outcomes. These polymorphisms in cyp2c19 gene and their impact in mace have been studied in southindian population only in limited number of studies.Methods:we studied 118 consecutive patients (mean age 55.7±10.7 years; 90% male) taking clopidogrel, with angiographically proven coronary artery disease for various genetic polymorphisms incyp2c19 gene. Relationship between loss of function mutation and clinical presentation with higher mace events including recurrent acute coronary syndromes, stent thrombosis were analyzed and genetic analysis. Results: out of 118 patients, 38 (32%) had normal genotype, 23 (20%) had loss offunction mutation( *2) the poor metabolizer type, and 57 (48%) had intermediate metabolizers (*2/*1). Final analyses included 118 patients, with 23 (20%) having loss of function. Seven patients developed stent thrombosis while on clopidogrel; all seven had loss of function mutationin cyp2c19 gene. Conclusion: we observed that the cyp2c19*2 and cyp2c19*1/*2 are the major determinants of clopidogrel efficacy. Acute stent thrombosis was observed in patients carrying cyp2c19*2 variant allele. In patients with an acute myocardial infarction who were receiving clopidogrel, with cyp2c19 loss-of-function alleles had higher rate of subsequent major cardiovascular events in comparison with normal genotype individuals.