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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Toll-like receptor 1 polymorphisms increase susceptibility to candidemia
Theo S Plantinga1, Melissa D Johnson, William K Scott
1Department of Medicine, Radboud University Nijmegen Medical Center, the Netherlands.
The Journal of Infectious Diseases
|February 4, 2012
Summary
Genetic variations in Toll-like receptor 1 (TLR1) single nucleotide polymorphisms (SNPs) increase susceptibility to candidemia in white populations by impairing immune responses. This finding highlights a genetic predisposition to this severe fungal infection.
Area of Science:
- Immunogenetics
- Infectious Diseases
Background:
- Candidemia is a life-threatening invasive fungal infection.
- Toll-like receptors (TLRs) mediate recognition of Candida species.
- Genetic variations in TLR signaling may influence candidemia susceptibility.
Purpose of the Study:
- To investigate the association between genetic variations in TLR signaling pathway genes and susceptibility to candidemia.
- To explore the functional consequences of identified genetic variations.
Main Methods:
- Genotyping of 13 single nucleotide polymorphisms (SNPs) in TLRs, MyD88, and Mal/TIRAP genes.
- Case-control study comparing 338 candidemia patients with 351 non-infected controls.
- Multivariable logistic regression and in vitro monocyte stimulation assays.
Main Results:
- Three TLR1 SNPs (R80T, S248N, I602S) were significantly associated with candidemia risk in white patients.
- These TLR1 polymorphisms impaired primary monocyte cytokine release.
- No significant associations were found for SNPs in other TLRs or signaling adaptors.
Conclusions:
- Nonsynonymous SNPs in TLR1 are linked to impaired TLR1 function and reduced cytokine responses.
- These TLR1 genetic variations predispose white individuals to candidemia.
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