Genetic Variants of Intron Region of Aquaporin AQP5 Gene and Development of Pulmonary Edema in Lung Infection Complicated by Septic Shock

• Published in: Obshchai͡a︡ reanimatologii͡a Vol. 12; no. 3; pp. 8 - 23
• Main Authors: Myazin, A. E., Chumachenko, A. G., Kuzovlev, A. N., Golubev, A. M., Moroz, V. V., Gaponov, A. M., Tutelian, A. V., Golubev, M. A., Pisarev, V. M.
• Format: Journal Article
• Language: English
• Published: Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia 2016
• Subjects: aqp5; aquaporins; gene polymorphism; pulmonary edema; septic shock; snp polymorphism
• ISSN: 1813-9779; 2411-7110
• DOI: 10.15360/1813-9779-2016-3-8-23

Purpose of the study. Determine the value of genetic variants of a single nucleotide polymorphic site rs3736309 of intron 3 of aquaporin5 (AQP5) gene in the course of critical illness in patients with documented pulmonary infection. Materials and methods. Patients with critical illness admitted to the intensive care units were examined during the course of treatment (n=86, age 27 to 82 years, mean age 53.20±14.34 years). Main diagnosis included malignancies (15%), peritonitis (16%) and necrotizing pancreatitis (37%). Patients developed nosocomial pneumonia (55%), acute respiratory distress syndrome (ARDS) (54%), septic shock (48%), ARDS combined with septic shock (33%). Bacterial species of Pseudomonas aeruginosa , Klebsiella pneumoniae, Acinetobacter baumannii, and/or Proteus mirabilis alone or in association were revealed in lavage fluid. DNA genotyping DNA was carried out using tetraprimer polymerase chain reaction (PCR). Statistical processing was performed using GraphPad InStat program (GraphPad, USA).Results. The distribution of frequencies of genotypes AA, GA and GG (AQP5, rs3736309) in cohort of patients corresponded to HardyWeinberg equilibrium (P=0.923) and was similar to frequencies of same alleles determined in a conditionally healthy Caucasian individuals (literature data) (P>0.05). In a subgroup of patients with septic shock and AQP5 AA (rs3736309) genotype the lower EVLWI values were found compared to patients with genotypes GG and GA with septic shock in spite of the same approach to treatment. The differences between genetically different subgroups of patients with septic shock were maintained throughout the life of the survey (P<0.05,days 1, 3, 5 and 7). Genetic variant AQP5 G+ (rs3736309) contributed to the development of pulmonary edema resistant to treatment (odds ratio, OR = 6,75; P=0.032). Only the subgroup of patients with septic shock and genotype G + (but not all patients or the subgroup of patients without septic shock of the same genotype) were characterized by significantly elevated levels of surfactant protein SPD in plasma compared to patients of genotype AQP5 AA with septic shock (P<0.05).Conclusion. In septic shock, the presence of homozygous variant allele A (AA) of AQP5 rs3736309 is a favorable factor for patients developing the pulmonary edema. The presence of allele AQP5 G (rs3736309) is a risk factor for developing severe pulmonary edema and unfavorable prognosis in spite of treatment.