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J Infect Dis. 2011 Mar 1;203(5):736-43. doi: 10.1093/infdis/jiq102. Epub 2011 Jan 17.

The Y238X stop codon polymorphism in the human β-glucan receptor dectin-1 and susceptibility to invasive aspergillosis.

Author information

1
Department of Medicine, Radboud University Nijmegen Medical Centre, The Netherlands.

Abstract

BACKGROUND:

Dectin-1 is the major receptor for fungal β-glucans on myeloid cells. We investigated whether defective Dectin-1 receptor function, because of the early stop codon polymorphism Y238X, enhances susceptibility to invasive aspergillosis (IA) in at-risk patients.

METHODS:

Association of Dectin-1 Y238X polymorphism with occurrence and clinical course of IA was evaluated in 71 patients who developed IA post hematopoietic stem cell transplantation (HSCT) and in another 21 non-HSCT patients with IA. The control group consisted of 108 patients who underwent HSCT. Functional studies were performed to investigate consequences of the Y238X Dectin-1 polymorphism.

RESULTS:

The Y238X allele frequency was higher in non-HSCT patients with IA (19.0% vs 6.9%-7.7%; P < .05). Heterozygosity for Y238X polymorphism in HSCT recipients showed a trend toward IA susceptibility (odds ratio, 1.79; 95% CI, .77-4.19; P = .17) but did not influence clinical course of IA. Functional assays revealed that although peripheral blood mononuclear cells with defective Dectin-1 function due to Y238X responded less efficiently to Aspergillus, corresponding macrophages showed adequate response to Aspergillus.

CONCLUSIONS:

Dectin-1 Y238X heterozygosity has a limited influence on susceptibility to IA and may be important in susceptible non-HSCT patients. This is partly attributable to redundancy inherent in the innate immune system. Larger studies are needed to confirm these findings.

PMID:
21242599
PMCID:
PMC3072717
DOI:
10.1093/infdis/jiq102
[Indexed for MEDLINE]
Free PMC Article

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