Plenary Lecture

Plenary Lecture

Single Nucleotide Polymorphism:
From Disease Susceptibility to Creativity

Dr. Victor Dosenko
Department of General and Molecular Pathophysiology
Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Currently, it is well known that risk and clinical severity of cardiovascular diseases as well as majority of other chronic pathologies depend on patient's genotype that determines functionality of all enzymatic systems. Individualization of universal defense and self-damaging mechanisms is determined mainly by genetic variations of some genes, so called single nucleotide polymorphism (SNP). Large number of SNPs that make every human unique in genetic and phenotypic features are described recently. We studied frequency of more than 20 SNPs in patients with myocardial infarction (492 cases) and in children with essential hypertension (157 cases) in Ukrainian population. Association between SNPs in eNOS (-786T/C), ACE (I/D) genes and myocardial infarction was established. Risk of essential hypertension is increased in patients with SNPs in eNOS (-786T/C and exon 7 Glu298/Asp), LMP2 (Arg60/His), PSMA6 (-8C/G), alpha-2 macroglobulin (I/D) and BNP (T-381/C) genes. Functional genetic investigations with use of RT-PCR, real-time PCR, fluorescent spectroscopy and other methods demonstrated that -786C/C promoter of eNOS most significantly affects the gene expression and eNOS activity. LMP2 Arg60/His polymorphism influences on trypsin-like and chymotrypsin-like activities of proteasome, but does not affect level of LMP2 mRNA. Our pharmacogenetic observations indicate that thrombolytic and cholesterol-lowering medications are more effective in patients with eNOS -786T/T genotype. Study of SNPs in highly qualified sportsmen (candidates and members of Ukrainian Olympic team) indicated negative correlation between track records and exon 7 Glu298/Asp eNOS, ACE (I/D), ACNT (R/X) and positive link with PPARG (Pro12/Ala) polymorphisms. To test hypothesis about influence of human genetic variability on mental (creative and cognitive) functions we realized investigation on determination of 13 SNPs frequency in 11 genes (NOS3, ACE, AGT, AGTR1, LMP2, HIF1A, A2M, XRCC1, PPARG, PSMA6 and BNP) that have not direct relation to psychic processes. With use of special psychological tests the level of creative and cognitive indicators was estimated in 73 adolescents. Correlation analysis allows to establish significant interrelation between number of variant alleles and level of creativity (r = 0.59, P < 0.05). Thus, obtained data indicate important impact of SNPs totality on formation of individual creativity and partly explain progressive spreading in human population of altered, in some ways pathological, gene variants that increase risk of cardiovascular diseases.

Brief Biography of the Speaker:
Since 2005 - Group Leader of General and molecular pathophysiology department of Bogomoletz Institute of Physiology. In 1995 he has obtained Master Degree in Medicine and PhD program in Pathophysiology department of Bogomoletz Ukranian Medical University. His scientific interests concerning to genetic mechanisms of myocardial infarction, role of allelic gene polymorphisms, proteasomal proteolysis, programmed cell death, etc. He is a co-author of 4-th monographs and more than 90 articles published in reviewed journals or presented at international conferences.

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