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CYP1A1, GCLC, AGT, AGTR1 gene–gene interactions in community-acquired pneumonia pulmonary complications

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Abstract

This study was conducted to establish the possible contribution of functional gene polymorphisms in detoxification/oxidative stress and vascular remodeling pathways to community-acquired pneumonia (CAP) susceptibility in the case–control study (350 CAP patients, 432 control subjects) and to predisposition to the development of CAP complications in the prospective study. All subjects were genotyped for 16 polymorphic variants in the 14 genes of xenobiotics detoxification CYP1A1, AhR, GSTM1, GSTT1, ABCB1, redox-status SOD2, CAT, GCLC, and vascular homeostasis ACE, AGT, AGTR1, NOS3, MTHFR, VEGFα. Risk of pulmonary complications (PC) in the single locus analysis was associated with CYP1A1, GCLC and AGTR1 genes. Extra PC (toxic shock syndrome and myocarditis) were not associated with these genes. We evaluated gene–gene interactions using multi-factor dimensionality reduction, and cumulative gene risk score approaches. The final model which included >5 risk alleles in the CYP1A1 (rs2606345, rs4646903, rs1048943), GCLC, AGT, and AGTR1 genes was associated with pleuritis, empyema, acute respiratory distress syndrome, all PC and acute respiratory failure (ARF). We considered CYP1A1, GCLC, AGT, AGTR1 gene set using Set Distiller mode implemented in GeneDecks for discovering gene-set relations via the degree of sharing descriptors within a given gene set. N-acetylcysteine and oxygen were defined by Set Distiller as the best descriptors for the gene set associated in the present study with PC and ARF. Results of the study are in line with literature data and suggest that genetically determined oxidative stress exacerbation may contribute to the progression of lung inflammation.

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Acknowledgments

This work was supported by a Grant of Presidium of the Russian Academy of Sciences program “Fundamental sciences for medicine”—2012, 2013; Fundamental Research Programs of the Russian Academy of Sciences “Biodiversity and dynamics of gene pools” (2006–2010); “Biological Diversity”, subdivision “Gene Pools and Genetic Diversity” (2011–2012).

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Authors and Affiliations

  1. N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Street, Moscow, 117971, Russia

    Lyubov E. Salnikova & Alexander V. Rubanovich

  2. V.A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences, 25 Petrovka Str., Build. 2, Moscow, 107031, Russia

    Lyubov E. Salnikova, Tamara V. Smelaya, Arkadiy M. Golubev & Viktor V. Moroz

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  1. Lyubov E. Salnikova
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Correspondence to Lyubov E. Salnikova.

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Salnikova, L.E., Smelaya, T.V., Golubev, A.M. et al. CYP1A1, GCLC, AGT, AGTR1 gene–gene interactions in community-acquired pneumonia pulmonary complications. Mol Biol Rep 40, 6163–6176 (2013). https://doi.org/10.1007/s11033-013-2727-8

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