TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation
Abstract
A bstract: 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.
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Numerous single-nucleotide polymorphisms within human Toll-like receptors and C-type lectin receptors have been identified as risk factors for fungal disease.
“Numerous single-nucleotide polymorphisms (SNPs) within human TLRs (TLR1 [11], TLR4 [12–15], TLR6 [11], among others) and CLRs (Dectin-1—in particular the Y238X SNP [16–18]; DC-SIGN, mannose receptor and mannose-binding lectin [19–22]) have been identified as risk factors for fungal disease.”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [11]
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- Authors
- KESH, S., MENSAH, N. Y., PETERLONGO, P., JAFFE, D., HSU, K., VAN DEN BRINK, M., O'REILLY, R., PAMER, E., SATAGOPAN, J., & PAPANICOLAOU, G. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- PAPANICOLAOU, G. A.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2005-12
- Volume
- 1062
- Issue
- 1
- Pages
- 95-103
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2022582881
- Cited by
- 208
- References
- 21
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 13 · 2015: 11 · 2014: 19 · 2013: 13 · 2012: 18
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- invasive aspergillosis, TLR1, TLR6, TLR4, single nucleotide polymorphisms, genetic susceptibility, allogeneic hematopoietic stem cell transplantation, Aspergillus fumigatus, immunocompromised patients, host genetic factors
- MeSH terms
- Alleles, Aspergillosis, DNA Mutational Analysis, Humans, Lung Diseases, Fungal, Prospective Studies, Retrospective Studies, Transplantation, Homologous, Logistic Models, Hematopoietic Stem Cell Transplantation, Amino Acid Substitution, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Toll-Like Receptor 1, Toll-Like Receptor 6
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