Genetic markers of predicting the development of pulmonary hypertension in cases of suppurative lung disease

BACKGROUND: The suppurative lung disease accompanied by destruction of lung tissueinclude the pleural empyema with or without fistula, the lung abscess with or without sequestration, the gangrenous abscess and several other less frequent conditions. The mortality among patients with this profile, considered as critical illness, remains high due to the development of life-threatening complications. The early stratification of patients by the risk of such complications can be useful for the physician when choosing the strategy for personalized treatment. The genetic variability of the AQP4 gene, the expression of which on the surface of cells in the lungs and in the immune system may have the pathogenetic meaning for the development of lung diseases and their complications, is the source of early markers for predicting the course of suppurative lung diseases. Previously we have demonstrated that the polymorphic gene variants of AQP4 rs1058427 are associated with the septic shock development and the outcome of sepsis. The contribution of AQP4 into the development of pulmonary hypertension was not investigated previously. AIM: To clarify the contribution of the AQP4 gene polymorphic variants and pathogenically relevant immune cells levels to the development of pulmonary hypertension in patients with the suppurative lung disease. METHODS: The research included the patients aged 18–87 years with suppurative lung diseases developed after the previous community-acquired pneumonia. Pulmonary hypertension was detected using the echocardiography (as demonstrated by the parameters of systolic pressure in the pulmonary artery ≥36 mm.Hg. and regurgitation rate of the tricuspid valve ≥2.9 m/sec). In all patients, the genotypes of AQP4 rs1058427 were determined. RESULTS: The presence of the AQP4 rs1058427 minor allele Т in patients with the suppurative lung disease was associated with the development of pulmonary hypertension and with the increase in blood monocytes count, with the presence of minor genotypes GT or TT of AQP4 rs1058427 indicating the high risk of developing the pulmonary hypertension. In cases of separately analyzing the subgroups of patients with or without the previous episodes of laboratory confirmed COVID-19, the statistical significance of the association remained only for the carriers of the allele Т and with no documented history of COVID-19 episode. CONCLUSION: The presence of the minor allele AQP4 rs1058427 (genotypes GT or TT) in the genotype of patients with the suppurative disease of the lungs has determined the increased risk of developing the pulmonary hypertension and the increased blood monocytes count.