Assessment of Association of rs2200733 SNP on Chromosome 4q25 with the Risk of the Development of Atrial Fibrillation in the Russian Population

The aim of our case-control study was to investigate the possible genetic association of the rs2200733 SNP on chromosome 4q25 with AF in the Russian population as this association has not been examined before in this ethnicity. Methods and Results: A total of 76 unrelated individuals diagnosed with AF and 73 control subjects without any cardiovascular pathology were included in this study. The diagnosis of AF was based on ECG and/or Holter ECG data following standard diagnostic criteria. We found that the TT genotype of the rs2200733 SNP was associated with a higher risk of AF (OR=1.4, 95% CI: 1.1-12.4). The homozygote minor rare allele genotype TT of the rs2200733 SNP tended to elevate the risk of lone AF development (OR=2.5, 95% CI: 1.2-19.5). A risk of secondary AF development did not depend on rs2200733 SNP on chromosome 4q25 (OR=0.5, 95% CI: 0.2-1.3). Conclusion: Our results provide additional evidence for the association between the rs2200733 (4q25) SNP on chromosome 4q25 and AF, emphasizing the need for further studies examining the role of this polymorphism in AF

ПАЛЬМИТИНОВАЯ, ОЛЕИНОВАЯ КИСЛОТЫ И ИХ РОЛЬ В ПАТОГЕНЕЗЕ АТЕРОСКЛЕРОЗА

On the basis of phylogenetic theory of general pathology, the cause of a noninfectious disease whose occurrence in a population is more than 5–7% is an impaired biological function or reaction to the environment. From the general biology viewpoint, high mortality rate related to cardio-vascular diseases and atherosclerosis (intercellular deficiency of polyenic fatty acids (PFA)) is just extinction of the Homo sapiens population upon adaptation to new environmental factors. The biological function of throphology (feeding) and biological reaction of exotrophy (external feeding) are impaired in several aspects, the major of which is nonphysiologically high dietary content of saturated fatty acids, primarily, of palmitic fatty acid (FA). The lipoprotein system formed at early stages of phylogenesis cannot transport and provide physiological deposition of great amounts of palmitic FA, which leads to the development of an adaption (compensatory) and accumulation disease. This results in hypermipidemia, impaired bioavailability of PFA to cells, compesatory production of humoral mediators from ω-9 eicosatrienoic mead FA, disorders in physiological parameters of cell plasma membrane and integral proteins, nonphysiological conformation of apoВ-100 in lipoproteins, formation of ligandless lipoproteins (biological litter) and impairments in the biological function of endoecology, utilization of ligandless lipoproteins in arterial intima by phylogenetically early macrophages that do not hydrolyze polyenic cholesterol esters, increase in the intensity of the biological reaction of inflammation, and destructive and inflammatory lesions in arterial intima of an atheromatosis or atherothrombosis type. Atheromatous masses are catabolites of PFA which were not internalized by phylogenetically late cells via receptor-mediated pathway.С позиций филогенетической теории общей патологии, если частота неинфекционного заболевания в популяции превышает 5–7%, причина кроется в нарушении биологических функций и биологических реакций in vivo в ответ на воздействие внешней среды. С позиций общей биологии высокий уровень смертности от сердечно-сосудистой патологии, атеросклероза (дефицита в клетках полиеновых жирных кислот (ПНЖК)) – это не более, чем вымирание части популяции Homo sapiens при адаптации к новым воздействиям внешней среды. Факторов нарушения биологической функции трофологии (питания), биологической реакции внешнего питания (экзотрофии) много, основным является афизиологично высокое содержание в пище насыщенных жирных кислот (ЖК), в первую очередь пальмитиновой. Образованная на ранних ступенях филогенеза система липопротеинов (ЛП) не в состоянии переносить к клеткам и физиологично депонировать столь большое количество пальмитиновой насыщенной ЖК; постепенно формируется болезнь адаптации (компенсации) и болезнь накопления. Это влечет за собой гиперлипидемию, нарушение биодоступности для клеток ПНЖК; компенсаторный синтез гуморальных медиаторов из ω-9 эйкозатриеновой мидовой ЖК; нарушение физиологичных параметров мембраны клеток, функции интегральных протеинов; афизиологичную конформацию апоВ-100 в ЛП, формирование безлигандных ЛП (биологического «мусора») и нарушение биологической функции эндоэкологии; утилизацию безлигандных ЛП в интиме артерий филогенетически ранними макрофагами, которые не гидролизуют полиеновые эфиры холестерина; повышение активности биологической реакции воспаления и деструктивно-воспалительное поражение интимы артерий по типу атероматоза или атеротромбоза. Атероматозные массы – катаболиты тех ПНЖК, которые не смогли рецепторным путем поглотить филогенетически более поздние клетки

Coulomb breakup of 17 Ne from the view point of nuclear astrophysics

6 pags., 5 figs. -- XII International Symposium on Nuclei in the Cosmos, August 5-12, 2012, Cairns, AustraliaBy the Coulomb breakup of 17Ne, the time-reversed reaction 15O(2p, γ) 17Ne has been studied. This reaction might play an important role in the rp process, as a break-out reaction of the hot CNO cycle. The secondary 17Ne ion beam with an energy of 500 MeV/nucleon has been dissociated in a Pb target. The reaction products have been detected with the LAND-R3B experimental setup at GSI. The preliminary differential and integral Coulomb dissociation cross section σCoul has been determined, which then will be converted into a photo-absorption cross section σphoto, and a two-proton radiative capture cross section σcap. Additionally, information about the structure of the 17Ne, a potential two-proton halo nucleus, will be received. The analysis is in progress.This project was supported by the German Federal Ministry for Education and Research (BMBF), EU(EURONS), EMMI-GSI, and HIC for FAI

Coulomb and nuclear excitations of narrow resonances in Ne-17

New experimental data for dissociation of relativistic 17Ne projectiles incident on targets of lead, carbon, and polyethylene targets at GSI are presented. Special attention is paid to the excitation and decay of narrow resonant states in 17Ne. Distributions of internal energy in the O15+p+p three-body system have been determined together with angular and partial-energy correlations between the decay products in different energy regions. The analysis was done using existing experimental data on 17Ne and its mirror nucleus 17N. The isobaric multiplet mass equation is used for assignment of observed resonances and their spins and parities. A combination of data from the heavy and light targets yielded cross sections and transition probabilities for the Coulomb excitations of the narrow resonant states. The resulting transition probabilities provide information relevant for a better understanding of the 17Ne structure

GENETIC PREDICTORS OF ATRIAL FIBRILLATION

Atrial fibrillation (AF) is the most common heart rhythm disturbance. It is believed that the primary form of AF is genetically determined in most cases, but the genetic component cannot be excluded in the secondary form of AF. AF is a heterogeneous disease and many authors proved its relationship with other genetic heart disease. In most cases, certain combinations of polymorphisms of different genes promote the development of AF. The study of genes of renin-angiotensin-aldosterone system (RAAS) is especially important, because the role of this system in AF pathogenesis is currently studding most intensively. These studies are of great practical interest, as associative effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the prevention of AF is revealed. RAAS blockers are able not only to reduce the risk of new-onset AF in hypertensive and normotensive patients but also prevent recurrence of AF. Furthermore, experimental studies showed that RAAS blockers prevent not only the remodeling of the left ventricle, and also the left atrium, pointing to the pathogenesis of AF. So, screening for susceptibility genes and the study of their polymorphism is currently an important focus in the study of AF

A SINGLE MECHANISM OF ACTION OF HYPOLIPIDEMIC DRUGS. BASIC PRINCIPLES OF PRIMARY PREVENTION OF ATHEROSCLEROSIS, ATHEROMATOSIS AND CORONARY SYNDROME

Irrespective of differences in mechanism of action, hypolipidemic drugs develop their effects according to a single algorithm. They normalize receptor-mediated uptake of polyenic fatty acids (PFA) by cells, thus restoring their functional, regulatory and structural state. Atherosclerosis is an in vivo pathology of each individual cell that cannot actively internalize PFA. Atherosclerosis is a syndrome of intracellular deficiency of ω-3 and ω-6 PFA. Compensatory production of humoral mediators (eicosanoids) from endogenous ω-9 С20:3 digomo-ү-linolenic unsaturated fatty acids (FA) renders them aphysiological and capable of impairing all functional processes in vivo, which results in a multilevel clinical manifestations of atherosclerosis and development of atheromatosis. Although atherosclerosis and atheromatosis are related to each other, they are different processes. Neither statins, nor other hypolipidemic drugs have any pleiotropic activity. They normalize cellular uptake of PFA which produce their intrinsic pleiotropic effects. As peroxisomal prolilferators, ω-3 eicosanoids oxidize excessive exogenous palmitic acid. Hypolipidemic effect of insulin is realized in conversion of entire palmitic FA synthesized in vivo from glucose into oleic FA. Hypolipidemic drugs are not the means of primary prevention of hyperlipidemia and atherosclerosis. This prevention should be based on normalization of the biological function of trophology and biological reaction of exotrophy and correction of quality and quantity of food according to real, quite limited functional possibilities ofHomo sapiens. The biological function of intellect plays an important role in primary prevention of hyperlipidemias and atherosclerosis

FIRST RUSSIA-BASED STUDY OF POLYMORPHISM rs2200733 CHROMOSOME 4q25 ASSOCIATION WITH DEVELOPMENT OF THE LONE ATRIAL FIBRILLATION

Atrial fibrillation (AF) is one of the most prevalent tachiarrhythmias, with at date non fully understood etiology. Recently, the attention is paid to genetic determinants of AF.Aim. To assess the role of rs2200733 polymorhpism on the chromosome 4q25 in development of AF in Russian population.Material and methods. Totally, 76 patients studied with AF, and control group, number 73 persons without cardiovascular pathology. All participants underwent laboratory and genetic investigations.Results. A statistically significant prevalence of genotype ТТ is found (21,21% vs 4,11%, р=0,015) and allele Т (34,85% vs 19,86%, р=0,03) in the group of patients with the lone AF comparing to the controls. Therefore, TT genotype and T allele of rs2200733 chromosome 4q25 could be predictors of unknown origin AF development

CLINICAL-GENETIC RISKOMETER FOR THE ISCHEMIC STROKE RISK ASSESSMENT IN ATRIAL FIBRILLATION

Aim. To assess genetic issues in the ischemic stroke development in AF and to invent an analytical programmed complex for genetic risk estimation of stroke development in a patient with AF.Material and methods. Totally 43 patients studied with AF and stroke in anamnesis, 78 — with AF and no stroke. Controls consisted of 188 persons without cardiovascular pathology. The participants underwent ECG, EchoCG, Holter ECG-monitoring, exercise test, TELAS, thyroid gland hormones analysis. For confirmation of the ischemic nature of stroke in participating probands we performed computed tomography of the brain. All participants also underwent molecular genetic testing.Results. According to the odds ratio, allele A polymorphism -455G>A of gene FGB increases the risk of ischemic stroke development in atrial fibrillation 1,7 times comparing to those patients without the allele; genotypes with the rare T allele in homoand heterozygous state of polymorphism 807С>Т of gene GPI? increases 2,5 times the risk of stroke in AF; presence of allele C polymorphism -5Т>С of gene GPI?? increases 1,9 times the risk of stroke comparing to its absence; presence of the rare genotypes allele C in homoand heterozygous state -5Т>С of gene GPI?? increases 2,3 times stroke risk; allele A of the polymorphism 10976G>A gene FVII decreases the risk of stroke 2,6 times. According to the results, there was a “Clinical-genetic riskometer of the ischemic stroke in AF” developed. Using this informational-analytic complex it is possible to estimate genetic risk of the stroke.Conclusion. Therefore, the study has shown that homozygous genotype AA of the rare polymorphism 455G>A gene FGB, heterozygous genotype СТ and homozygous genotype ТТ of the rare polymorphism allele 807С>Т gene GPI?, heterozygous genotype TC and homozygous genotype CC by the rare allele polymorphism -5Т>С gene GPI?? are defined as genetic predictors of ischemic stroke development in atrial fibrillation. Allele А of polymorphism 10976G>A gene FVII is protective against ischemic stroke in patients with AF. Knowing the parameters of genetic assessment in AF, it is possible to calculate genetic risk of ischemic stroke development in AF via invented by us a “Clinical-Genetic riskometer of ischemic stroke in AF”

GLYCOPROTEIN INTEGRIN ALPHA POLYMORPHISM AND ACUTE CEREBROVASCULAR EVENTS IN THE FAMILIES OF PATIENTS WITH ATRIAL FIBRILLATION

Aim. To assess the associations between the polymorphism of the glycoprotein integrin alpha (