title: Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia.
abstract: Infectious complications continue to be one of the major causes of morbidity and mortality in patients with acute myeloid leukemia (AML). Several single-nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) can affect the genetic susceptibility to infections or even sepsis. We sought to investigate the impact of different SNPs on the incidence of developing sepsis and pneumonia in patients with newly diagnosed AML following induction chemotherapy. We analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) gene in a cohort of 155 patients with AML who received induction chemotherapy. The risk of developing sepsis and pneumonia was assessed by multiple logistic regression analyses. The presence of the TLR2 Arg753Gln polymorphism was significantly associated with pneumonia in AML patients (odds ratio (OR): 10.78; 95% confidence interval (CI): 2.0-58.23; P=0.006). Furthermore, the cosegregating TLR4 polymorphisms Asp299Gly and Thr399Ile were independent risk factors for the development of both sepsis and pneumonia (OR: 3.55; 95% CI: 1.21-10.4, P=0.021 and OR: 3.57, 95% CI: 1.3-9.86, P=0.014, respectively). To our best knowledge, this study represents the first analysis demonstrating that polymorphisms of TLR2 and TLR4 influence the risk of infectious complications in patients with AML undergoing induction chemotherapy.
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schnetzke
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Spies-Weisshart
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Yomade
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Rachow
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schrenk
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Jena, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Glaser
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Department of Hematology and Oncology, Klinik für Innere Medizin II (Abteilung Hämatologie und Internistische Onkologie), Universitätsklinikum Jena, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Scholl
mesh_terms: D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy; D011014:Pneumonia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D018805:Sepsis / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4