title: TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation.
abstract: Toll-like receptors (TLRs) transmit signals in response to Aspergillus fumigatus conidia and hyphae. In this preliminary study, we examined the association between single nucleotide polymorphisms (SNPs) in TLR1, TLR4, and TLR6 genes and development of invasive aspergillosis (IA) in 127 allogeneic hematopoietic stem cell transplant recipients consisting of 22 patients with IA and 105 unaffected control subjects. The following SNPs and their pairwise interactions were considered in the model: TLR1 (239G > C, 743A > G, 914A > T, 1805G > T), TLR4 (896A > G, 1196C > T), and TLR6 (359T > C, 745C > T, 764C > T). No association was found between donor SNP and the risk of IA. Analysis of recipient SNP data showed that the presence of TLR1 239G > C (Arg80 > Thr) or the presence of both TLR1 743A > G (Asn248 > Ser) and TLR6 745C > T (Ser249 > Pro) is associated with IA (odds ratio = 1.30, 95% confidence interval = 1.13 to 1.50; P < .001). Further analyses using a prospective cohort may enable us to identify TLR polymorphisms associated with the susceptibility to IA within a defined interval among immunocompromised patients.
authors.affiliation: Department of Medicine, Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave., Box 9, New York, NY 10021, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kesh
authors.forename: Nana Yaa
authors.initials: NY
authors.lastname: Mensah
authors.forename: Paolo
authors.initials: P
authors.lastname: Peterlongo
authors.forename: Dana
authors.initials: D
authors.lastname: Jaffe
authors.forename: Katharine
authors.initials: K
authors.lastname: Hsu
authors.forename: Marcel
authors.initials: M
authors.lastname: VAN DEN Brink
authors.forename: Richard
authors.initials: R
authors.lastname: O'reilly
authors.forename: Eric
authors.initials: E
authors.lastname: Pamer
authors.forename: Jaya
authors.initials: J
authors.lastname: Satagopan
authors.forename: G A
authors.initials: GA
authors.lastname: Papanicolaou
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D001228:Aspergillosis / Q000235:genetics* / Q000276:immunology; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008172:Lung Diseases, Fungal / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012189:Retrospective Studies; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D014184:Transplantation, Homologous
chemical_list: C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051216:Toll-Like Receptor 6