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№3' 2016
CARDIOLOGYInternational Medical Journal, Vol. 22., Iss. 3, 2016, P. 11−15.
GENETIC ASPECTS OF CORONARY ARTERY DISEASE RISK AND THE EFFICACY OF ANTITHROMBOTIC THERAPY
L. T. Malaya National Institute of Therapy NAMS of Ukraine, Kharkiv, Ukraine
The knowledge of the genetic factors predisposing to the disease and its complications can have important prognostic significance and be used both before the appearance of any clinical or biochemical signs of the disease and when choosing the drugs and treatments modalities. The study of allelic polymorphism of the hemostatic system genes in patients with coronary artery disease (CAD) as well as in healthy individuals in the general population allowed to find alleles that are in varying degrees associated with predisposition to development of this disease in different ethnic groups. To determine the frequency of allelic variants of C50T PTGS1 gene polymorphism and relation of polymorphism with clinical, biochemical and functional aspirin resistance in patients with coronary artery disease, patients with chronic forms of CAD (stable angina, myocardial infarction) were examined against a background of standard therapy. The patients were divided into aspirin resistant whose cardiovascular adverse events and those clinically sensitive to ACK without complications. As a criterion of the level of biochemical aspirin resistance 11−dehydro−thromboxane B2, functional AR −− total arachidonate index and ADP−induced platelet aggregation was determined. Genotyping of a polymorphic site of S50T gene PTGS1 (rs3842787) was performed by polymerase chain reaction followed by analysis of restriction fragment length. The probability of ACVE development for mutant T−allele COG−1 polymorphism patients was significantly higher (Odds ratio =3.39; 95 % CI [1.39−8,77], p = 0.019), than for C−allele patients. A significant relationship of mutant T−allele C50T polymorphism gene COX−1 with the index of arachidonate−induced platelet aggregation (p = 0.0007), with the malonic dialdehyde (MDA) (p = 0.024) and low density lipoprotein cholesterol (LDL) cholesterol levels (p = 0.049) was revealed. The presence of the mutant C−allele of the gene polymorphism T1565S was significantly associated with LDL level, urine 11−dehydro TxB2 levels and the level of (NO2 + NO3). The findings demonstrate that the presence of mutant alleles of polymorphism C50T PTGS1 gene and polymorphism T1565S ITGB3 gene is significantly associated with coronary artery disease pathogenetic factors that can contribute to a more severe course of the disease and increase the risk of adverse cardiovascular events.
Key words: coronary artery disease, aspirin resistance, gene polymorphism.