Features of clinical and laboratory indicators in alcoholic liver disease in combination with arterial hypertension depending on T786C polymorphism of the eNOS gene

Abstract

The goal of the work. Assess the relationship between eNOS gene genotypes (T786C) and some clinical and laboratory parameters in patients with alcoholic liver disease (ALD) in combination with arterial hypertension (AH).Material and methods. 97 patients diagnosed with AHP were examined: 62 patients with ALD with AH (group A) and 35 patients with ALD (group B). Serum content of C-reactive protein, tumor necrosis factor-α (TNFα), transforming growth factor-β1 (TGFβ1), interleukin-10 (IL-10), 8-isoprostane, D-dimer was determined by enzyme-linked immunosorbent assay. The functional state of the endothelium was assessed by the content in the blood of stable metabolites of nitrogen monoxide (nitrites / nitrates), endothelin-1 (ET-1), intercellular adhesion molecules-1 (ICAM-1). Total blood coagulation potential (plasma recalcification time), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), plasma fibrinogen levels, antithrombin III (ATIII) activity, factor XIII (F XIII) activity was determined by traditional methods. Spontaneous platelet aggregation was also studied. To determine the eNOS mutation (T786C), rs2070744 used a protocol with oligonucleotide primers using the method of allele-specific PCR.Results. When studying the frequency of genotypes by the polymorphic variant of the eNOS gene (T786C), it was found that the frequency of TT genotype among patients with ALD with hypertension was 46.8%, CT - 57.1% and SS - 17.2%. Among patients with ALD, the following distribution of genotypes was found: TT - 25.7%, ST - 57.1% and SS - 17.2%. We found a significant difference between the group of patients with ALD with AH and the isolated group of ALD by TT genotype. It was found that the level of ET-1 and the intercellular adhesion molecule (ICAM-1) were significantly higher in patients with ALD with AH by TT genotype compared with the isolated course of ALD. However, the level of total nitric oxide in the combined course of ALD with hypertension was lower than in patients with ALD without hypertension in the presence of this genotype. At the same time, in the combined course of ALD and hypertension, the level of systemic inflammation and oxidative stress is associated with the TT genotype by a polymorphic variant of the eNOS gene (T786C). When studying the state of hemostasis in the combined course of ALD and hypertension, it was found that APTT for the TT genotype was 17.7% higher than in group B. This indicator also had a difference in the middle group between the TT and CT genotypes (by 13.1%) and TT and CC (by 28.3%). The level of D-dimer between groups A and B also had a significant difference in the TT genotype (higher by 14.7% for the combination of ALD and AH). Spontaneous platelet aggregation was significantly higher by 7.7% in patients with ALD with hypertension by TT genotype. In the latter group of patients, factor XIII was significantly lower by 12.6% compared with the group of patients with ALD. Indicators such as plasma recalcification time, prothrombin index and time, thrombin time did not differ significantly between groups of patients.Conclusion. The development of hypertension in patients with ALD is associated with the presence of a homozygous TT genotype for a polymorphic variant of the eNOS gene (T786C). It was found that in patients with ALD with hypertension by TT genotype higher levels of ET-1 and intercellular adhesion molecules ICAM-1 are observed at a lower level of total nitric oxide compared with patients with ALD. The most probable differences in systemic inflammation (IL-10, CRP, TGFβ1) and oxidative stress marker (8-isoprostane) are characteristic of the TT genotype for the polymorphic variant of the eNOS gene (T786C) in patients with ACP with hypertension compared with the isolated course of ALD. Hemostasis parameters such as APTT, antithrombin III, D-dimer, spontaneous platelet aggregation and factor XIII were associated with the TT genotype in patients with ALD with hypertension by the polymorphic variant of the eNOS gene (T786C).