PO05 Demystifying Early Onset Coronary Artery Disease By Genetic Testing Of Cyp2c8*3 And Cyp2j2*7 Polymorphisms In The Bulgarian Population

Background Genomic studies give insight into molecular pathways and pathogenesis of disease and have contributed to our understanding of CAD. Coronary microvascular dysfunction (CMD) is a major contributor to ischemic heart disease (IHD), acting both independently and together with atherosclerosis. Cytochrome P450 (CYP) 2J2 is expressed in the vascular endothelium and it metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs). The EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. Inter-individual differences in the action of these substances might be important in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and myocardial infarction (MI). Purpose We analyzed the impact of a genetic variant in CYP2C8 on CAD and of MI in Bulgarian population. We conducted a case-control study to determine whether the common genetic variation rs890293 (CYP2J2*7) in CYP2J2 gene was associated with the risk of CMD and MI. Methods We analyzed 99 patients with MI and 377 controls for a potential correlation of the CYP2J2 polymorphism G-50T and a history of MI. 96 of these 99 patients were tested for the presence of polymorphisms CYP2C8 To evaluate the genotypes of the samples real time PCR with predesigned TaqMan SNP Genotyping Assays (Applied Biosystem) for rs890293 (Assay ID: C___9581699_20) was used. Studied the variation of allele polymorphism CYP2J2 * 7 and CYP2C8 * 3 on the balance of Hardy-Weinberg (Hardy-Weinberg) and the frequency of the T allele with c2 test. Results The results from investigation of the genetic markers for polymorphisms CYP2J2*7 и CYP2C8*3 in participants who had survived myocardial infarction were analyzed. To this purpose, data about the genetic polymorphisms of a group of healthy controls were used. The group of survival of myocardial infarction included 99 people. Of these, 96 were also investigated for the presence of polymorphism CYP2C8*3. The control group for polymorphism CYP2J2*7 included 377 subjects, and that for polymorphism – 363 subjects. Conclusions The resulting p-values for both polymorphism (for CYP2C8 * 3, p = 0.7901 and p = 0,0670 CYP2J2 * 7) indicates that the distribution of T allele CYP2C8 * 3 with high probability close to balance Hardy Weinberg, than in the CYP2J2 * The chances for people with T-allele polymorphism in the CYP2C8 * 3, MI occur on average 1.7 times higher than those who did not carry this allele. CI of OR (2,874 ÷1,0334) with 95% probability. CI indicated that it could be argued with a 95% probability that the presence of T allele in CYP2C8 * 3 increases the risk of MI. The analysis of data obtained p=0,9489, OR=0,9717, CI (0,4034 ÷ 2,3404) showed no indications T allele CYP2C8 * 3 has completely different chances for the occurrence of stroke in men and women. The analysis of results shows that polymorphism CYP2C8 * 3 is important for the occurrence of MI compared with CYP2J2 * 7 participants in the survey.