Allelic polymorphism of endothelial NO-synthase gene and its functional manifestations.

Abstract

Investigation of the mechanisms of phenotypic realization of allelic polymorphism of the eNOS gene has shown that the level of eNOS mRNA and activity of this enzyme in platelets depends from genotype. We identified a T(-786)-->C polymorphism in the promoter region, a variable number of tandem repeats (4a/4b) in intron 4 and the G(894)-->T polymorphism in exon 7 of the eNOS gene in isolated human platelets. We measured eNOS mRNA in isolated platelets by reverse transcription-PCR and eNOS enzyme activity by fluorimetric detection system FCANOS-1 using diaminofluorescein diacetate (DAF-2A). It was shown that the level of eNOS mRNA is the lowest for the -786C/C promoter genotype. In exon 7 homozygotes (894T/T) the level of RNA is lower than in normal homozygotes (894G/G), but higher than in heterozygotes (894G/T). The eNOS activity in platelets is lower in carriers of the 786C/C promoter genotype than in normal homozygotes (2.1 times; P=0.03), and lower comparing to heterozygotes (2.9 times; P>0.05). The eNOS activity accompanying the 894T/T variant of exon 7 is also lower than in normal homozygotes (P>0.05). Regarding the polymorphism in intron 4 - the enzyme's activity is lower in carriers of the 4a/4a genotype comparing to normal homozygotes (1.7 times; P>0.05) and lower than in heterozygotes (1.9 times; P>0.05). These results allow one to conclude that the T(-786)-->C polymorphism of the eNOS gene promoter most significantly affects the gene expression and eNOS activity.

<b><i>NOS3</i></b> Gene rs1799983 and rs2070744 Polymorphisms in Patients with Unstable Angina

“…Alternately, other authors have not observed clinical associations with disease [15,16]. Dosenko et al [17] reported that eNOS mRNA levels are lower in eNOS mutant homozygotes rs1799983 TT than in homozygotes GG. eNOS activity, ac-companying the TT variant, is also lower when compared to GG homozygotes.…”

Effects of eNOS rs1799983 and ACE rs4646994 polymorphisms on the therapeutic efficacy of salvianolate injection in Chinese patients with coronary heart disease

“…The results of the present study are consistent with the notion that eNOS 894G/T and ACE I/D variations may contribute to interindividual response variability in CHD patients treated with salvianolate: patients with the T allele and D allele were more likely to be poor responders to S. miltiorrhiza . Dosenko et al . reported that eNOS mRNA levels are lower in eNOS mutant homozygotes (894T/T) than in normal homozygote (894G/G), but higher than in heterozygotes (894G/T).…”

Influence of endothelial nitric oxide synthase T-786→C-promoter polymorphism on integral parameters of functional condition of arterial vessels

“…Contrariwise in work of Erbs S. et al an opposite evidence is presented that carriers of rare promoter gen-otype variant (C/C genotype) have for 44% lower frequency of coronary and mammary arteries dilatation in response to acetylcholine administration (doppler velosimetry data) [16]. Taking into account presented intelligence and our own data about association of SNP Ò -786 →Ñ in promoter of NOS3 gene with probability of acute coronary syndrome appearance [10,12], it was aimed to determine the influence of this SNP upon the integral features of arterial vessels state using the test for reactive hyperemia and detecting blood vessel wall stiffness performing ultrasonic estimate of pulse wave arrival frequency.…”