[Pathophysiologic aspects of endothelial NO-synthase genetic polymorphism].
Information about fourteen allelic variants of promoter, exons and introns of a gene of endothelial NO-synhase (eNOS) dealing with their role in a susceptibility to cardio-vascular diseases has been reviewed. Data of the populational genetic studies, performed in different regions of the world, were analysed to show the interrelation between an availability of on allele in the genome and a risk of ischemic heart disease. The main attention was focussed on the clarification of a relation between some allelic variants of the gene and functional (biochemical) properties of the protein, encoded by this gene, as well as on two principal mechanisms of realization of the pathological allelic variants in eNOS gene: 1) forming the protein in an insufficient quantity or with an altered activity (an interrupted transcription, and stability of informational RNA, formation of a cathalitically deficient protein); 2) an increased protein degradation (due to an acidic hydrolysis or an enhanced proteasomal proteolysis). In practical aspect, the most important problem, according to the point of view of the authors, is that of searching the pharmaco-therapeutical remedies, able to influence the different stages of the molecular-biological realization of an altered eNOS gene (transcription, translation, posttranslational modifications and degradation). Clarification of the above pathogenetic mechanisms will open broad perspectives in constructing therapeutical schemes for individuals possessing the pathological alleles of this gene.
Dosenko
V Ie
VIe
Bogomoletz Institute of Physiology, National Academy of Science, Kiev, Ukraine.
Zahoriĭ
V Iu
VIu
Moĭbenko
O O
OO
Parkhomenko
O M
OM
D003327:Coronary Disease / Q000201:enzymology / Q000235:genetics; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic
D019001:Nitric Oxide Synthase