The Y238X Stop Codon Polymorphism in the Human beta-Glucan Receptor Dectin-1 and Susceptibility to Invasive Aspergillosis

LYA Chai, MGJ de Boer, WJFM van der Velden, TS Plantinga, AB van Spriel, C Jacobs, CJM Halkes, Alieke Vonk, NM Blijlevens, JT van Dissel, PJ Donnelly, BJ Kullberg, J Maertens, MG Netea

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Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)736-743
Number of pages8
JournalJournal of Infectious Diseases
Volume203
Issue number5
DOIs
Publication statusPublished - 2011

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  • EMC MM-04-28-01

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