Genetic variations in the oxidative stress related genes are associated with pulmonary complications in community-acquired pneumonia

This study was conducted to establish the possible contribution of functional gene polymorphisms in the oxidative stress related genes to the development of community-acquired pneumonia (CAP) complications. CAP subjects (n=350) were genotyped for 16 polymorphic variants in the genes of xenobiotics detoxification CYP1A1, AhR, GSTM1, GSTT1, ABCB1, redox-status SOD2, CAT, GCLC, and vascular homeostasis ACE, AGT, AGTR1, NOS3, MTHFR, VEGFa. The multilocus model, which included six or more risk alleles in the CYP1A1, GCLC, AGT and AGTR1 genes, was associated with pleuritis, empyema, acute respiratory distress syndrome (ARDS), all pulmonary complications together and acute respiratory failure. Genetically mediated correlation between clinical conditions in CAP patients is shown in Table 1. In silico analysis with Set Distiller mode [1] identified N-acetylcysteine (P=1.08E-08) and oxygen (P=1.92E-06) as the best descriptors for the considered gene set. Acute infections of the airways are associated with oxidative stress, which enhances viscosity of bronchial mucus, reduces the mucociliary clearance rate and expedites lung disease aggravation and progression [2]. N-acetylcysteine is a well-known mucolytic and antioxidant drug, an indirect precursor of glutathione [3]. The results of the study indicate that pneumonia aggravation up to destructive intrapulmonary complications and ARDS is mediated by polymorphisms in oxidative stress-related genes.