PATHOPHYSIOLOGICAL ASPECTS OF ENDOTHELIAL NO-SYNTASE GENETIC POLYMORPHYSM
V.E. Dosenko, V.Yu. Zagoriy, A.A. Moibenko, A.N. Parchomenko
Bogomoletz Institute of Physiology, National Academy of Science, Kiev, Ukraine
Abstract
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 desease.
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 catalitically 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 molecularbiological
realization of an altered eNOS gene (transcription,
translation, posttranslational modifications and degradation).
Clarification of the obove pathogenetic mechanisms will open
broad perspectives in constructing therapeutical schemes for
individuals possessing the pathological alleles of this gene.
Keywords:
GENETIC POLYMORPHYSM
References
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