L.G. Voronkov, N.G. Gorovenko, M.R. Ilnytska.T−786→C polymorphism of the endothelial nitric oxide synthase gene in patients with chronic heart failure, depending on the insulin resistance

The aim – to assess polymorphic variants of T−786→C gene of endothelial NO-synthase depending on presence of insulin resistance (IR) in patients with systolic chronic heart failure (CHF).

Material and methods. We have examined 107 patients (pts) with CHF of II–IV NYHA class with left ventricular systolic dysfunction without diabetes, with coronary heart disease or dilated cardiomyopathy. The pts have undergone general clinical studies, echocardiography, flow-mediated vasodilatory response (FMD) of arteria brachialis. Insulin was determined by the automatic enzyme immunoassay method. Index HOMA ≥ 2.77 was taken into account as a criterion for IR. To determine plasma level of TNF-α we have used enzyme immunoassay test system. The molecular genetic study of polymorphism T−786→C gene of endothelial NO-synthase based on method of the polymerase chain reaction determined polymorphic variants of T−786→C eNOS gene according to modified procedures.

Results. IR phenomenon has been found in 45 pts (42 %) with chronic heart failure. About a third of pts (33 of 107) had the HOMA index value between 3.0 or higher. The main clinic-demographic, hemodynamic, echo parameters have not shown a statistically significant difference between pts with CHF with or without IR. However, pts with CHF and IR had significantly lower FMD (5.40 (4.63; 7.95) %) of arteria brachialis than pts without IR, where correspondingly (7.99 (5.21; 11.50) %; Р=0.033). Among 104 examined pts with CHF (three patients refused genetic testing for religious reasons) the promoter polymorphism genotype TT T–786→C eNOS gene has been observed in 43.2 % (n=19) pts with IR, and in 31.7 % (n=19) without IR; there have been 45.5 % of TC heterozygotes (n=20) with IR, and 55.0 % (n=33) without IR; the so-called rare genotype CC has been observed in both groups almost equally.

Conclusions. Insulin resistance has been detected in 42 % patients with CHF and left ventricular systolic dysfunction. Among examined pts with systolic CHF frequency of genotypes TT, TC, CC T−786→C gene of endothelial NO-synthase has not differed significantly in the groups with and without IR. Poor flow-mediated vasodilatory response of arteria brachialis in pts with CHF and the presence of phenomenon of IR has been associated with higher levels of TNF-α and uric acid in the blood serum.

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