title: Impact of NOD2 polymorphisms on infectious complications following chemotherapy in patients with acute myeloid leukaemia.
abstract: We sought to investigate the relationship between polymorphisms of the NOD2 gene and infectious complications following intensive induction chemotherapy in patients with acute myeloid leukaemia (AML). We hypothesised that single nucleotide polymorphisms (SNPs) of the NOD2 gene are associated with a higher rate of infections during the phase of severe neutropenia. In 131 AML patients receiving induction therapy, the presence of the three most frequent polymorphisms of NOD2 (Arg702Trp, Gly908Arg, Leu1007fsinsC) was analysed. SNP analyses by means of genomic PCR incorporating fluorescence-labelled probes with characteristic melting curves were performed using the LightCycler platform. Our data suggest a significantly lower probability of mucositis or enteritis in AML patients lacking any of the three evaluated NOD2 polymorphisms. Furthermore, bloodstream cultures of AML patients carrying either a missense or a frameshift mutation of NOD2 were significantly more frequently tested positive concerning Streptococcus spp. In contrast, the presence of NOD2 polymorphisms had no impact on such important infectious complications as systemic inflammatory response syndrome or sepsis, the rate of central venous catheter infections or the incidence of pneumonia including fungal infections. Our data represent one of the first reports investigating the impact of polymorphisms of the innate immune system on infectious complications in patients with neutropenia following chemotherapy. A correlation between NOD2 polymorphisms and infectious events in AML patients is demonstrated.
authors.affiliation: Abteilung Hämatologie/Internistische Onkologie, Klinik für Innere Medizin II, Jena University Hospital, Erlanger Allee 101, Jena, Germany.
authors.forename: Olaposi
authors.initials: O
authors.lastname: Yomade
authors.forename: Bärbel
authors.initials: B
authors.lastname: Spies-Weisshart
authors.forename: Anita
authors.initials: A
authors.lastname: Glaser
authors.forename: Ulf
authors.initials: U
authors.lastname: Schnetzke
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Sebastian
authors.initials: S
authors.lastname: Scholl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001424:Bacterial Infections / Q000209:etiology*; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D016867:Immunocompromised Host; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009181:Mycoses / Q000209:etiology; D009363:Neoplasm Proteins / Q000235:genetics*; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D009363:Neoplasm Proteins; D053473:Nod2 Signaling Adaptor Protein