Abstract
Introduction: The course of heart failure (HF) and its progression is associated with co-morbidities, genetic factors and a dynamics of a number of biomarkers. The low triiodothyronine syndrome (LT3S) is observed in some patients with HF. Extremely little data are available in the literature regarding the effect of b-adrenoreceptors (b-AR) genes polymorphisms on the development of LT3S and many contradictory results about their association with HF course. This encourages new research in this area.
The aim: To study the relationship of b-adrenergic receptors gene polymorphisms with low triiodothyronine syndrome in patients with a heart failure.
Materials and methods: 354 patients with HF on a background of postinfarction cardiosclerosis were included to the study. At 89 (25.1%) patients LT3S was diagnosed. The course of HF was studied for 2 years. Mean levels of thyroid stimulating hormone (TSH), free T3f and T4f were evaluated. Genotyping of 4 single nucleotide polymorphisms (Gly389Arg of b1-AR gene, Ser49Gly of b1-AR gene, Gln27Glu of b2-AR gene and Ser275 of GNb3 gene) was performed by polymerase chain reaction. Genetic and epidemiological analysis was performed using the SNPStats program.
Results: The risk of LT3S in patients with HF increases with homozygous G/G variant of Gln27Glu polymorphism of the b2-AR gene (odds ratio (OR) = 2.21 [1.05-4.28], p = 0.037, recessive model of inheritance). There was a tendency to increase the risk of LT3S development in the presence of the genotype C / T of the Ser275 polymorphism of the GNb3 gene (OR = 1.75 [0.99-3.07], p = 0.054, an over-dominant model). The genotype C / G of the Gln27Glu polymorphism of the b2-AR gene was associated with a decreased risk of LT3S development (OR = 0.54 [0.30-0.98], p = 0.037, over-dominant model). Patients with HF carriers the A allele (A / GA / A) of the Ser49Gly polymorphism of the b1-AR gene have a lower risk of repeated hospitalization due to HF decompensation (OR = 0.50 [0.26-0.97], p = 0.032, dominant model). There was a tendency to increase the risk of re-hospitalization in the G-allele (C / G-G / G) variant of the Gln27Glu polymorphism of the b2-AR gene (OR = 1.68 [0.98-2.87], p = 0.057, dominant heredity model). At patients with HF in combination with LT3S the risk of re-hospitalization increases at C / G variant of the Gln27Glu polymorphism of b2-AR gene (OR = 1.25 [0.85-1.82], p = 0.025, over-dominant model).
Conclusions: The results suggest that congenital genetic alterations in b-adrenergic pathways may be associated with the development of LT3S in patients with HF and the features of the HF course.
Keywords: low triiodothyronine syndrome, b1-adrenoreceptors, b2-adrenoreceptors, G-protein, heart failure, single-nucleotide polymorphisms, risk.