Molecular Medicine and Diagnostics

Biography

Biography: Alexander N Parkhomenko

Abstract

In 492 patits with acute coronary syndromes (ACS) we studied polymorphisms of different genes - NOS3 (eNOS), LMP2, LMP7, HIF1α, ACE, PPARG, PSMA6, AGT, MGP, AGTR1, BMP, A2M, MMP2, MMP9 и XRCC1. Polymorphisms of NOS3 and MGP were found as markers of the disease and may be used for individual pathophysiological profile characteristics and prediction of pharmacological agents effects. Frequency of eNOS Т-786С promoter polymorphism and influence of this polymorphism on reactive hyperemia and arterial stiffness were determined. Higher degree of brachial arteries diameter increase in response to ischemia in patients with Т/Т genotype: 8,03  0,71% compared to 5,55  0,92 % in Т/С (Р<0.05) and 5,30  1,21 % in С/С genotypes (P<0.05). Speed of pulse wave spreading on carotid-radial and carotid-femoral arteries segments was also depended on patients genotype: in Т/Т genotype was 9,10  0,15 and 8,68  0,26 correspondingly, in Т/С - 9,38  0,18 and 8,74  0,21, and in С/С carriers - 9,71  0,22 and 10,02  0,71 (P<0.05). Obtained data indicate on significant influence of Т-786С polymorphism on integral parameters of functional status of arterial vessels in ACS patients. Matrix g-carboxyglutamic acid protein (MGP) is known be a potent inhibitor of calcification in blood vessels and is highly expressed on calcified atherosclerotic plaques in humans; we defined a significant association between the G–7→A promoter polymorphism of the MGP gene and ACS. From clinical point of view it is important to understand transformation of genetic data into prediction of disease complication and possibility to improve effectiveness of medication. We found that efficacy of early statin therapy in patients with ACS is determined by polymorphism of eNOS gene promoter : -786TT genotype of eNOS gene promoter was associated with decreased risk of recurrent ischemic events (myocardial infarction -MI and post-MI angina) and acute heart failure in statin treated patients. While there were no benefits of early statin treatment in patients with TC, CC and both (TC+CC) genotypes. A new class of small noncoding RNAs known as microRNAs (miRNAs) has recently been proposed to play a critical role in genetic regulation of physiological and pathological processes. Changes in levels of microRNA-1, -155, -210, -208a, -208b, and -499 in blood plasma, platelets and monocytes of patients with acute MI have been tested. The results of research allows us to make the assumption that higher level of microRNA-155 in monocytes can be a marker of MI development. The indicators of favorable MI follow-up correlated with the microRNA-155 level - higher level was associated with better kidney fuction (higher GFR, lower level of creatinine) and less frequency of heart failure. In conclusion, our studies confirm the possibility of individualized clinical assessment of patients with ACS, implementation of a new standards for tradional management and development of novel treatment by using modern genetic and epigenetic approaches.