A Polymorphism in the Catalase Gene Promoter Confers Protection against Severe RSV Bronchiolitis

Respiratory syncytial virus (RSV) infection is associated with oxidative lung injury, decreased levels of antioxidant enzymes (AOEs), and the degradation of the transcription factor NF-E2-related factor 2 (NRF2), a master regulator of AOE expression. Single nucleotide polymorphisms (SNPs) in AOE and NRF2 genes have been associated with various lung disorders. To test whether specific NRF2 and/or AOE gene SNPs in children with RSV lower respiratory tract infection were associated with disease severity, one hundred and forty one children <24 month of age with bronchiolitis were assessed for seven AOE and two NRF2 SNPs, and data were correlated with disease severity, which was determined by need of oxygen supplementation and intensive care support. One SNP in the promoter region of the catalase gene, rs1001179, which is associated with higher enzyme expression, was significantly underrepresented (p = 0.01, OR 0.38) among patients with moderate to severe RSV bronchiolitis, suggesting a protective effect against disease severity. Our results suggest that increasing catalase expression/activity could exert a protective role in the context of RSV infection and represent a potential novel therapeutic target to ameliorate viral-induced lung disease.

[1]  H. Spratt,et al.  A Polymorphism in the Catalase Gene Promoter Confers Protection Against Severe RSV Bronchiolitis , 2018 .

[2]  R. Garofalo,et al.  Respiratory syncytial virus induces NRF2 degradation through a promyelocytic leukemia protein ‐ ring finger protein 4 dependent pathway , 2017, Free radical biology & medicine.

[3]  M. Lucero,et al.  Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study , 2017, The Lancet.

[4]  T. Ivanciuc,et al.  Respiratory syncytial virus infection down-regulates antioxidant enzyme expression by triggering deacetylation-proteasomal degradation of Nrf2. , 2015, Free radical biology & medicine.

[5]  Hye-Youn Cho,et al.  Functional polymorphisms in Nrf2: implications for human disease. , 2015, Free radical biology & medicine.

[6]  R. Garofalo,et al.  Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity , 2014, Influenza and other respiratory viruses.

[7]  C. Bai,et al.  Gene polymorphisms and chronic obstructive pulmonary disease , 2013, Journal of cellular and molecular medicine.

[8]  S. Fuke,et al.  Bronchiolar epithelial catalase is diminished in smokers with mild COPD , 2012, European Respiratory Journal.

[9]  M. Hebert-Schuster,et al.  Catalase polymorphisms and metabolic diseases , 2012, Current opinion in clinical nutrition and metabolic care.

[10]  P. Burney,et al.  PM10-induced Hospital Admissions for Asthma and Chronic Obstructive Pulmonary Disease: The Modifying Effect of Individual Characteristics , 2012, Epidemiology.

[11]  T. Sigsgaard,et al.  Genetic polymorphisms in antioxidative enzymes are associated to forced expiratory volume in 1 s (FEV1) in smokers independently of asthma , 2012, The clinical respiratory journal.

[12]  A. Kurosky,et al.  Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis. , 2011, American journal of respiratory and critical care medicine.

[13]  V. Parviainen,et al.  Network analysis of single nucleotide polymorphisms in asthma , 2010, Journal of asthma and allergy.

[14]  Pedro A Piedra,et al.  LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity , 2010, Pediatrics.

[15]  R. Garofalo,et al.  Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes. , 2009, American journal of respiratory cell and molecular biology.

[16]  A. Kong,et al.  Molecular mechanisms of Nrf2‐mediated antioxidant response , 2009, Molecular carcinogenesis.

[17]  S. Kleeberger,et al.  Oxidants and the pathogenesis of lung diseases. , 2008, The Journal of allergy and clinical immunology.

[18]  W James Gauderman,et al.  Ozone, oxidant defense genes, and risk of asthma during adolescence. , 2008, American journal of respiratory and critical care medicine.

[19]  M. Chan-yeung,et al.  Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients , 2006, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[20]  R. Garofalo,et al.  Reactive Oxygen Species Mediate Virus-induced STAT Activation , 2004, Journal of Biological Chemistry.

[21]  J. Crapo,et al.  Superoxide dismutases in the lung and human lung diseases. , 2003, American journal of respiratory and critical care medicine.

[22]  R. Garofalo,et al.  Macrophage Inflammatory Protein-1α (Not T Helper Type 2 Cytokines) Is Associated with Severe Forms of Respiratory Syncytial Virus Bronchiolitis , 2001 .

[23]  R. Garofalo,et al.  Oxidant Tone Regulates RANTES Gene Expression in Airway Epithelial Cells Infected with Respiratory Syncytial Virus , 2001, The Journal of Biological Chemistry.

[24]  U. de Faire,et al.  A common functional C-T substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reporter gene transcription and is correlated to blood catalase levels. , 2001, Free radical biology & medicine.

[25]  I. Fridovich.  Biological effects of the superoxide radical. , 1986, Archives of biochemistry and biophysics.

[26]  L. Vávřová,et al.  Human catalase, its polymorphisms, regulation and changes of its activity in different diseases. , 2014, Folia biologica.

[27]  J. Stockman.  Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis , 2012 .

[28]  I. Rahman.  Redox signaling in the lungs. , 2005, Antioxidants & redox signaling.

[29]  Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal Antibody, Reduces Hospitalization From Respiratory Syncytial Virus Infection in High-risk Infants. , 1998, Pediatrics.