[Polymorphism of eNOS and iNOS Genes and Chronic Heart Failure in Patients With Ischemic Heart Disease].
URGENCY: Despite substantial progress in the treatment of coronary heart disease (CHD) and chronic heart failure (CHF) prognosis in these conditions remains extremely serious. This warrants their timely prevention and early detection. Aim. To study influence of inducible NO synthase (iNOS) (CCTTT)n, Glu298Asp and diallel polymorphism in the fourth intron (4a/4b polymorphism) of endothelial NO synthase gene (eNOS gene) on the state of endothelial function and risk of development of CHF in patients with CHD.


METHODS
165 patients with CHD were studied (121 male and 44 female, mean age 56.7 + or - 5.3 years). Vasomotor endothelial function was evaluated using ultrasound method in the reactive hyperemia and trinitroglycerol tests. Genotypes were identified using RFLP analysis of PCR products. Control group consisted of 114 persons (54 male and 60 female, mean age 53.2 + or - 4.9 years).


RESULTS
It was determined that the number of repeats of polymorphic locus (CCTTT)n of the iNOS gene and Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state were associated with the risk of development of CHD and class of severity of CHF clinical manifestation. In addition Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state was associated with the severity and unfavorable development of CHF. The endothelial-dependent dysfunction was more severe in homozygotes of Glu allele of the polymorphic locus Glu298Asp of eNOS gene than in carrier of allele 298Asp. Associations between polymorphic variant of VNTR intron 4 gene eNOS and CHF with the risk of development and endothelial dysfunction were not found.


CONCLUSIONS
An association between polymorphism of iNOS gene (CCTTT)n, eNOS gene (Glu298Asp) with development of CHD and severity of CHF was shown. The polymorphism of eNOS gene (Glu298Asp) was associated with endothelial dysfunction.
Tepliakov
A T
AT
Research Institute for Cardiology of the Research Centre of RAMN Siberian Branch, ul. Kievskaya 111, 634012 Tomsk, Russia.
Shilov
S N
SN
Berezikova
E N
EN
Iakovleva
N F
NF
Maianskaia
S D
SD
Popova
A A
AA
Luksha
E B
EB
Voronina
E N
EN
Torim
Iu Iu
IuIu
Karpov
R S
RS
D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006333:Heart Failure / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000097:blood / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D014664:Vasodilation / Q000502:physiology
D004247:DNA; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III