POLYMORPHISM OF GENES OF THE β-ADRENORECEPTION SYSTEM AND THE EFFECT OF LEVOTYROXINE ON THE COURSE OF HEART FAILURE IN PATIENTS WITH NON-TOXIC GOITER
About the author:
Pyvovar S. M., Rudyk Yu. S., Lozyk T. V., Galchinska V. Yu., Bondar T. M.
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
Heart failure (HF) is an important medical, social and economic problem. The incidence, occurance and mortality from this pathology are still high today, and the prognosis remains unfavorable. Optimizing existing and developing new treatment strategies is important for HF. The interest in the role of thyroid hormones in HF has increased over the last decade. Experimental and clinical studies have shown that thyroid hormones counteract the progression of HF, probably due to genomic and non-genomic effects in the myocardium, heart vessels and the whole body. In modern standards of HF treatment, the use of thyroid hormones, in the absence of hypothyroidism, is not recommended. In addition, at non-toxic goiter (NG), the most common thyroid pathology, levothyroxine (LT) is a recognized treatment strategy, even in the absence of organ hypofunction. This makes it possible to study the effects of LT in HF. Aim: to study the associations of gene polymorphisms of the β-adrenoreception system with the effect of levothyroxine on the course of heart failure in patients with non-toxic goiter. Object and research methods. In the study 218 patients with heart failure on the background of post-infarction cardiosclerosis were included. All patients were diagnosed with NG. 109 patients received LT in connection with NG. Genotyping was performed for 4 polymorphisms (Gly389Arg of the β1 -receptor gene (β1 -АR), Ser49Gly of the β1 -АR gene, Gln27Glu of the β2 -АR gene and Ser275 of the β3-subunit of G-protein (GNβ3 )) using polymerase chain reaction. Echocardioscopy and ultrasound of the thyroid gland were performed. We studied the course of heart failure for 2 years. Results. Use of LT in connection with NG reduces the risk of re-hospitalization (RH) of patients with heart failure (Odds ratio (OR) = 0.490 (0.281-0.857), p = 0.018). A tendentious decrease in the risk of achieving a combinedendpoint was revealed (by 27.9%, p = 0.074). The analysis did not reveal any reliable associations of the effect of the use of LT on the frequency of RH with the polymorphism of genes of the β-adrenoreception system. The division of patients into groups by LT dose (according to the ROC analysis) revealed that the use of the drug at a dose of > 0.53 μg/kg in homozygous carriers of the C-allele of Gln27Glu polymorphism (c.79C> G) of the β2-AR gene leads to reduce the risk of RH over two years (OR = 0.09 (0.02-0.48)). In the subgroup of patients with a heterozygous (C / G) genotype, an increase in the risk of an adverse course of heart failure (an increase in the incidence of RH, OR = 3.82 (1.29-11.31), p = 0.0087) was detected in the absence of LT treatment. No reliable association of LT effect on the course of heart failure with other polymorphisms of the β-adrenoreceptor system genes were revealed. Conclusions. Congenital genetic differences in the pathways of β-adrenoreception may modulate effects of levothyroxine. The use of this drug at a dose of > 0.53 μg/kg in homozygous carriers of the C allele of the Gln27Glu polymorphism (c.79C> G) of the β2-adrenoreceptor gene reduces the risk of re-hospitalization due to decompensation of the heart failure for two years.
heart failure, non-toxic goiter, gene, polymorphism, β-adrenoreceptors, levothyroxine.
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Publication of the article:
«Bulletin of problems biology and medicine» Issue 4 Part 2 (154), 2019 year, 181-188 pages, index UDK 616.12-008.46-085:575.174.015.3:616.441-006.5