الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Coronary Heart disease (CHD) is a complex chronic inflammatory disease, characterized by remodeling and narrowing of the coronary arteries. It remains the leading cause of death globally. There are many causes implicating its occurrence, the most common is coronary artery atherosclerosis. Risk factors for CHD can be categorized into non-modifiable (age, sex, family history) and modifiable (smoking, hypertension, diabetes, dyslipidemia, obesity, physical inactivity) and modification of some of these factors can reduce the risk of CHD.Dual antiplatelet therapy consisting of aspirin and clopidogrel is the cornerstone of care in the management of patients after PCI. Clopidogrel works by irreversibly inhibiting P2Y12 receptor, an adenosine diphosphate chemoreceptor on platelet cell membranes, while aspirin is a COX-1 inhibitor, preventing the production of TBXA2, which plays an important role in platelet aggregation. Clopidogrel is a prodrug requiring biotransformation into the active metabolite by the hepatic cytochrome 450 system, especially the CYP2C19 enzyme. Paraoxonase 1 (PON1) is also suggested to be a rate-limiting enzyme in this biotransformation. Antiplatelet drug response displays considerable interindividual variability resulting in suboptimal therapy. Genetic factors account for up to 70% of impaired drug response. Gene studies have identified loss-of-function CYP2C19 variants as CYP2C19*2 and CYP2C19*3 to be associated with a diminished pharmacologic responsePharmacogenetics is the study of the role of genetics in drug response, it offers the personalization of treatment according to the genotype. In the present study we tried to apply pharmacogenetics through studying the SNPs believed to be responsible for response variability. Genotyping by RFLP- PCR was done for CYP2C19*2, CYP2C19*3 and PON1 genes polymorphism. Also ADP and AA agonists were used to assess platelet function testing by LTA. These tests were done on 25 selected Egyptian patients admitted to cardiology Department at Alexandria Main University Hospital with documented CAD subjected to elective PCI with 1 stent at least taking 75 mg/day clopidogrel and 100 mg/day aspirin for 1 month at least post PCI. In addition to 25 contols with matched age and sex not on dual antiplatelet in the last month.Cases were subjected to history taking, clinical examination, ECG and Echocardiography. Laboratory investigations including routine investigations, bleeding time, platelet aggregometry by LTA and genotyping by RFLP- PCR were done. No significant difference were found in demographic data between cases and controls. Although bleeding time was normal in both cases and controls, there was significant difference in cases denoting aspirin effective therapy.This study detected that 4% and 8% of the cases had increased response to AA and ADP respectively. It also showed the distribution of the three genotypes as follows; CYP2C19*2 G/G was 72%, CYP2C19 *2 G/A was 20% and CYP2C19 *2 A/A was 8%, while CYP2C19*3 G/G was 80%, CYP2C19 *3 G/A was 20% with no CYP2C19 *3 A/A detected. In addition, PON1 QQ was 36%, PON1 QR was 40% and PON1 RR was 24%