RT Journal Article
T1 Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection.
A1 Sainz, Juan
A1 Lupiáñez, Carmen Belén
A1 Segura-Catena, Juana
A1 Vazquez, Lourdes
A1 Ríos, Rafael
A1 Oyonarte, Salvador
A1 Hemminki, Kari
A1 Försti, Asta
A1 Jurado, Manuel
K1 Aspergilosis
K1 Ensayo de Inmunoadsorción Enzimática
K1 Moléculas de Adhesión Celular
K1 Lectinas Tipo C
K1 Enfermedades Pulmonares Fúngicas
K1 Mananos
K1 Reacción en Cadena de la Polimerasa
K1 Polimorfismo Genético
K1 Polimorfismo de Nucleótido Simple
K1 Receptores de Superficie Celular
AB The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1(rs3901533 T/T) and Dectin-1(rs7309123 G/G) genotypes and DC-SIGN(rs4804800 G), DC-SIGN(rs11465384 T), DC-SIGN(7248637 A) and DC-SIGN(7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR = 4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR = 2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1(rs3901533_T) allele and Dectin-1(rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1(rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis.
PB Public Library of Science
YR 2012
FD 2012-02-27
LK http://hdl.handle.net/10668/1344
UL http://hdl.handle.net/10668/1344
LA en
NO Sainz J, Lupiáñez CB, Segura-Catena J, Vazquez L, Ríos R, Oyonarte S, et al. Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection. PLoS ONE. 2012; 7(2):e32273
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 7, 2025