title: Association between TLR2/TLR4 gene polymorphisms and COPD phenotype in a Greek cohort.
abstract: BACKGROUND
  Considering that the innate immune system plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that functional single-nucleotide polymorphisms (SNPs) of innate immune genes affect the disease phenotype and prognosis.
  
  
  OBJECTIVE
  To elucidate the contribution of common functional TLR2 and TLR4 SNPs and genotypic deficiency of the mannose-binding lectin (MBL) protein, both as single parameters and in combination, in Greek COPD patients.
  
  
  RESULTS
  In a cohort of 114 Greek COPD patients, we confirmed that the presence of TLR4-D299G or TLR4-T399I SNPs was significantly associated with an earlier COPD stage (p = 0.003 and p = 0.009, respectively). In comparison, the absence of any analyzed polymorphism, including those of TLR2-R753Q and genotypic MBL deficiency, was significantly associated with a more severe disease phenotype, characterized by more frequent exacerbations (p = 0.045).
  
  
  CONCLUSIONS
  Our findings support the notion that the presence of innate immune SNPs, such as functional polymorphisms of TLRs along with MBL deficiency, might exert a protective effect on the COPD phenotype, similar with other immune-mediated disorders.
authors.affiliation: School of Health Sciences, Faculty of Medicine, Department of Immunology & Histocompatibility, University of Thessaly, 41500, Larissa, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Apostolou
authors.affiliation: School of Health Sciences, Faculty of Medicine, Respiratory Department, University of Thessaly, Larissa, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Kerenidi
authors.affiliation: School of Health Sciences, Faculty of Medicine, Department of Immunology & Histocompatibility, University of Thessaly, 41500, Larissa, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Michopoulos
authors.affiliation: School of Health Sciences, Faculty of Medicine, Respiratory Department, University of Thessaly, Larissa, Greece.
authors.forename: K I
authors.initials: KI
authors.lastname: Gourgoulianis
authors.affiliation: Department of Cardiology, Pneumology and Intensive Care Medicine, Clinic for Internal Medicine I, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-9066-5262
authors.initials: M
authors.lastname: Noutsias
authors.affiliation: School of Health Sciences, Faculty of Medicine, Department of Immunology & Histocompatibility, University of Thessaly, 41500, Larissa, Greece.
authors.forename: A E
authors.initials: AE
authors.lastname: Germenis
authors.affiliation: School of Health Sciences, Faculty of Medicine, Department of Immunology & Histocompatibility, University of Thessaly, 41500, Larissa, Greece. maspel@med.uth.gr.
authors.forename: M
authors.initials: M
authors.lastname: Speletas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D065840:Protective Factors; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016540:Smoking Cessation
chemical_list: D037601:Mannose-Binding Lectin
keywords: Chronic obstructive pulmonary disease; Genetic polymorphisms; Mannose-binding lectin protein deficiency; Toll-like receptor 2; Toll-like receptor 4