title: Polymorphisms of Dectin-1 and TLR2 Predispose to Invasive Fungal Disease in Patients with Acute Myeloid Leukemia.
abstract: BACKGROUND
  Patients with acute myeloid leukemia (AML) who undergo induction chemotherapy are at high risk for invasive fungal disease (IFD). Dectin-1, a C-type lectin family member represents one of the most important pattern recognition receptors of the innate immune system and single nucleotide polymorphisms (SNPs) in the Dectin-1 gene have been associated with an increased risk of infectious complications. We sought to investigate the impact of three different Dectin-1 SNPs and one TLR2 SNP on developing IFD in 186 adult patients with newly diagnosed AML following anthracycline-based induction chemotherapy.
  
  
  METHODS
  Genotyping of Dectin-1 SNPs (rs16910526, rs3901533 and rs7309123) and TLR2 SNP (rs5743708) was performed by TaqMan method and pyrosequencing. IFD was defined according to the EORTC/MSG consensus guidelines. Multiple logistic regression analyses were applied to evaluate the association between the polymorphisms and the occurrence of pulmonary infections. Dectin-1 expression studies with SNP genotyped human monocytes were performed to elucidate susceptibility to IFD following chemotherapy.
  
  
  RESULTS
  We could demonstrate that patients carrying the Dectin-1 SNP rs7309123 G/G (n = 47) or G/G and C/G (n = 133) genotype revealed a significant higher risk for developing both pneumonia in general (adjusted odds ratio (OR): 2.5; p = 0.014 and OR: 3.0, p = 0.004) and pulmonary IFD (OR: 2.6; p = 0.012 and OR: 2.4, p = 0.041, respectively). Patients carrying the TLR2 SNP rs5743708 (R753Q, GA/AA genotype, n = 12) also revealed a significantly higher susceptibility to pneumonia including IFD. Furthermore, Dectin-1 mRNA expression in human monocytes was lower following chemotherapy.
  
  
  CONCLUSIONS
  To our best knowledge, this study represents the first analysis demonstrating that harbouring polymorphisms of Dectin-1 (rs7309123) or TLR2 (rs5743708) represents an independent risk factor of developing IFD in patients with AML undergoing induction chemotherapy.
authors.affiliation: Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Baerbel
authors.initials: B
authors.lastname: Spies-Weisshart
authors.affiliation: Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schrenk
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Wittig
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Glaser
authors.affiliation: Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Scholl
authors.affiliation: Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schnetzke
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008172:Lung Diseases, Fungal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics*; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D009363:Neoplasm Proteins; D051195:Toll-Like Receptor 2; C546929:CLEC7A protein, human; D000099181:Dectin-1; C495342:TLR2 protein, human