Sainz, JuanLupiáñez, Carmen BelénSegura-Catena, JuanaVazquez, LourdesRíos, RafaelOyonarte, SalvadorHemminki, KariFörsti, AstaJurado, Manuel2013-10-232013-10-232012-02-27Sainz J, Lupiáñez CB, Segura-Catena J, Vazquez L, Ríos R, Oyonarte S, et al. Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection. PLoS ONE. 2012; 7(2):e32273http://hdl.handle.net/10668/1344Journal Article; Research Support, Non-U.S. Gov't;The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1(rs3901533 T/T) and Dectin-1(rs7309123 G/G) genotypes and DC-SIGN(rs4804800 G), DC-SIGN(rs11465384 T), DC-SIGN(7248637 A) and DC-SIGN(7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR = 4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR = 2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1(rs3901533_T) allele and Dectin-1(rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1(rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis.enAspergilosisEnsayo de Inmunoadsorción EnzimáticaMoléculas de Adhesión CelularLectinas Tipo CEnfermedades Pulmonares FúngicasMananosReacción en Cadena de la PolimerasaPolimorfismo GenéticoPolimorfismo de Nucleótido SimpleReceptores de Superficie CelularMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::AgedMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Mycoses::Hyalohyphomycosis::AspergillosisMedical Subject Headings::Organisms::Eukaryota::Fungi::Mitosporic Fungi::Aspergillus::Aspergillus fumigatusMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Glycoproteins::Cell Adhesion MoleculesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques::Enzyme-Linked Immunosorbent AssayMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Lectins::Lectins, C-TypeMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Mycoses::Lung Diseases, FungalMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Polysaccharides::MannansMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds RatioMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain ReactionMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, GeneticMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell SurfaceMedical Subject Headings::Phenomena and Processes::Mathematical Concepts::Probability::RiskMedical Subject Headings::Named Groups::Persons::Age Groups::Adolescentresearch article22384201open access10.1371/journal.pone.00322731932-6203PMC3288082