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Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection

Sainz, Juan; Belen Lupianez, Carmen; Segura-Catena, Juana; Vazquez, Lourdes; Rios, Rafael; Oyonarte, Salvador; Hemminki, Kari LU ; Försti, Asta LU and Jurado, Manuel (2012) In PLoS ONE 7(2).
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
7
issue
2
publisher
Public Library of Science
external identifiers
  • wos:000302918500071
  • scopus:84857548629
ISSN
1932-6203
DOI
10.1371/journal.pone.0032273
language
English
LU publication?
yes
id
148d230c-7aed-4db7-9061-7da61860b4c6 (old id 2571389)
date added to LUP
2012-06-01 08:55:10
date last changed
2017-09-24 04:13:23
@article{148d230c-7aed-4db7-9061-7da61860b4c6,
  abstract     = {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.},
  author       = {Sainz, Juan and Belen Lupianez, Carmen and Segura-Catena, Juana and Vazquez, Lourdes and Rios, Rafael and Oyonarte, Salvador and Hemminki, Kari and Försti, Asta and Jurado, Manuel},
  issn         = {1932-6203},
  language     = {eng},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection},
  url          = {http://dx.doi.org/10.1371/journal.pone.0032273},
  volume       = {7},
  year         = {2012},
}