Epoxyeicosatrienoic acids (EETs) are important vasoactive products of arachidonic acid metabolism with a wide range of biological actions in the cardiovascular system. The present study investigated whether single nucleotide polymorphisms (SNP) of genes coding cytochrome P450 2C subfamily, enzymes involved in biosynthesis of EETs, are associated with the risk of coronary heart disease (CHD). A total of 1255 unrelated Russian subjects comprising 561 patients with angiographically diagnosed CHD and 694 age- and sex-matched healthy subjects were included in the study. DNA samples from all study participants were genotyped for six common SNPs rs7909236, rs1934953 of CYP2C8, rs9332242, rs4918758 and rs61886769 of CYP2C9 and rs4244285 of CYP2C19 using by the Mass-ARRAY 4 system. SNP rs4918758 of CYP2C9 was associated with decreased risk of CHD (codominant model) at a borderline significance with odds ratio adjusted for sex and age 0.61 (95% CI: 0.41-0.92, P=0.038, Q=0.20). SNP rs9332242 of CYP2C9 showed a trend towards association with increased CHD risk in cigarette smokers (P=0.049, Q=0.29). Log-likelihood ratio test (LRT) pointed out epistatic interactions between rs9332242 and rs61886769 of CYP2C9 (codominant model, P=0.02), however, this P-value did not survive after correction for multiple tests. Bioinformatic analysis revealed a regulatory potential for a majority of the investigated SNPs. Our preliminary results demonstrate that polymorphisms of genes encoding CYP2C subfamily represent potential genetic markers of CHD susceptibility. Further studies are required to substantiate the contribution of these genes to the disease risk.

Enzymes CYP4A11 and CYP4F2 are involved in biosynthesis of vasoactive 20-hydroxyeicosatetraenoic acid and may contribute to pathogenesis of coronary artery disease (CAD). We investigated whether polymorphisms of the CYP4A11 and CYP4F2 genes are associated with the risk of CAD in Russian population. DNA samples from 1323 unrelated subjects (637 angiographically confirmed CAD patients and 686 age- and sex-matched healthy individuals) were genotyped for polymorphisms rs3890011, rs9332978, and rs9333029 of CYP4A11 and rs3093098 and rs1558139 of CYP4F2 by using the Mass-ARRAY 4 system. SNPs rs3890011 and rs9332978 of CYP4A11 were associated with increased risk of CAD in women: OR = 1.26, 95% CI: 1.02–1.57, P = 0.004, and Q = 0.01 and OR = 1.45, 95% CI: 1.13–1.87, P = 0.004, and Q = 0.01, respectively. Haplotype G-C-A of CYP4A11 was associated with increased risk of CAD (adjusted OR = 1.41, 95% CI: 1.12–1.78, and P = 0.0036). Epistatic interactions were found between rs9332978 of CYP4A11 and rs1558139 of CYP4F2 (P interaction = 0.025). In silico analysis allowed identifying that SNP rs9332978 is located at a binding site for multiple transcription factors; many of them are known to regulate the pathways involved in the pathogenesis of CAD. This is the first study in Europeans that reported association between polymorphism rs9332978 of CYP4A11 and susceptibility to coronary artery disease.

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Проведено исследование функционального состояния организма 197 пациентов с острой коронарной патологией (ОКП) в возрасте 40-65 лет с помощью аппаратно-программного комплекса «Динамика-Омега-М». Выявлено, что на госпитальных и постгоспитальных этапах реабилитации показатели функционального состояния (ФС) больных ОКП были ниже нормы, однако между больными нестабильной стенокардией и острым инфарктом миокарда имелся ряд различий в период с 3-х суток до 6-го месяца по значению показателей адаптации сердечно-сосудистой системы (А), центральной регуляции (С) и интегральному показателю здоровья (Н). Динамические изменения на фоне реабилитации были однонаправленны и проявлялись в увеличении значений показателей А, С, D, Н и снижении показателя В у больных как нестабильной стенокардией, так и острым инфарктом миокарда. Ключевые слова: нестабильная стенокардия, острый инфаркт миокарда, функциональное состояние, программно-аппаратный комплекс «Омега-М» Peculiarities of functional state (FS) in 197 patients (aged 40-65 years old) with an acute coronary pathology was assessed by the Dynamics-Omega-M software and hardware system. It was revealed that at hospital and post-hospital rehabilitation, the parameters of FS in patients with acute coronary pathology were under the norm. However, the number of differences was registered between the 3rd day and 6th months of the study in values of parameters of adaptation of the cardiovascular system (A), central regulation (C), and the integral index of health (H) between patients with unstable angina and acute myocardial infarction. Dynamic changes during the period of rehabilitation were unidirectional and manifested in an increase of the values of A, C, D, H parameters and a decrease in B parameter in patients with both unstable angina and acute myocardial infarction.