Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection Sáinz Pérez, Juan Lupiañez, Carmen Segura Catena, Juana Vazquez, Lourdes Ríos, Rafael Oyonarte Gómez, Salvador Hemminki, Kari Försti, Asta Jurado Chacón, Manuel 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-1rs3901533 T/T and Dectin-1rs7309123 G/G genotypes and DC-SIGNrs4804800 G, DC-SIGNrs11465384 T, DC-SIGN7248637 A and DC-SIGN7252229 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-1rs3901533_T allele and Dectin-1rs7309123_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-1rs7309123 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. 2024-10-08T08:41:34Z 2024-10-08T08:41:34Z 2012-02-27 journal article Sainz J, Lupiáñez CB, Segura-Catena J, Vazquez L, Ríos R, et al. (2012) Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection. PLoS ONE 7(2): e32273. doi:10.1371/journal.pone.0032273 https://hdl.handle.net/10481/95667 10.1371/journal.pone.0032273 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Plos One