Abstract
Introduction. Chronic heart failure is a multifactorial disease, an important role in the pathogenesis of which is played by disorders of the functions of mitochondria and energy metabolism in cardiomyocytes, as well as a significant contribution is made by genetic factors that affect the severity and prognosis of the disease. It has been shown that there may be some influence of genetic variants of NQO1 on the metabolism of coenzyme Q and the severity of chronic heart failure.
The aim of the study – to study the effect of the C609T variant of the NADP(H)-quinone oxidoreductase 1 (NQO1) gene (rs1800566) on the content of total coenzyme Q in blood plasma and the functional activity of mitochondria of mononuclear leukocytes in the blood.
Material and methods. The research included 53 patients with chronic heart failure who had experienced myocardial infraction. Mitochondrial membrane potential was evaluated by flow cytometric method using the propidium iodide and 3,3′-dihexyloxacarbocyanine iodide (DiOC6(3)). The determination of the coenzyme Q levels was done using the high performance liquid chromatography with UV detection. Genotyping of single nucleotide substitutions in the structure of the NQO1 gene was carried out by PCR-PDRF analysis (polymerase chain reaction with subsequent analysis of polymorphism of the lengths of the restition fragments).
Results. A comparative analysis of the total CoQ content in blood plasma did not reveal significant differences in the CoQ content in groups with different NQO1 genotypes. However, there was a tendency to lower rates in groups with the C/T and T/T genotypes. There were also no differences in the number of DiOC-positive cells in homozygotes with the C/C genotype and heterozygous C/T. There was a significantly significant content of DiOC-negative cells in the group with the T/T genotype in comparison with the C/C+C/T genotype.
Conclusion. In the absence of NQO1 activity, a decrease in mitochondrial membrane potential was observed in homozygotes with the T/T genotype. The additional use of KoI drugs can compensate for the developing mitochondrial dysfunction and contribute to the preservation of the functional state of the mitochondria. Determination of genetic variants of NQO1 can be useful in choosing treatment tactics (the expediency of prescribing ubidecarenone drugs).
Authors and affiliations
O.A. Lobanova(1) , L.B. Gaikovaya(2), O.V. Sirotkina(1, 3, 4), G.A. Kukharchik(1), A.I. Ermakov(5), K.A. Zagorodnikova(1)
1-Almazov National Medical Research Centre, Akkuratova st. 2, Saint-Petersburg, 197341, Russian Federation;
2-North-Western State Medical University named after I.I. Mechnikov, Kirochnaya st. 41, Saint-Petersburg, 191015, Russian Federation;
3-Pavlov First Saint Petersburg State Medical University, L'va Tolstogo str. 6–8, Saint-Petersburg, 197022, Russian Federation;
4-Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»,
mkr. Orlova roshcha 1, Gatchina, Leningradskaya Oblast, 188350, Russian Federation;
5-Clinical Laboratory Department St. Petersburg City AIDS Center,
nab. Obvodnyi channel, 179, Saint-Petersburg, 190103, Russian Federation
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