TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation.
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.
Kesh
Sandra
S
Department of Medicine, Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave., Box 9, New York, NY 10021, USA.
Mensah
Nana Yaa
NY
Peterlongo
Paolo
P
Jaffe
Dana
D
Hsu
Katharine
K
VAN DEN Brink
Marcel
M
O'reilly
Richard
R
Pamer
Eric
E
Satagopan
Jaya
J
Papanicolaou
G A
GA
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
C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051216:Toll-Like Receptor 6