To explore the potential consequences of Dectin-1 rs7309123 SNP, Dectin-1 mRNA expression was measured in 21 healthy donors and was correlated with genotypes. Our results showed that subjects harbouring GG genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers (p,0.001; Figure 2 ). These results further supported our hypothesis suggesting that Dectin-1 rs7309123_G allele may disrupt binding sites for potential transcription factors. The MDR analysis of the SNPs tested revealed statistically significant interactions. Two SNPs (rs1024611 and rs4264222) were excluded from the MDR analysis as they were in LD with other SNPs using a cut-off value of r 2 ,0.80 in our sample set. The best interaction models selected by the TuRF filter algorithm along with its testing accuracy and cross-validation consistency are shown in Table 4 . The overall best model with the highest crossvalidation consistency (CVC) consisted of a model that included the CCL2 rs4586 , Dectin-1 rs3901533 , CCR2 rs3918358 and Dectin-2 rs7134303 SNPs. This model had a significant testing accuracy of 0.7735 (permutation p,0.001) and a cross-validation consistency of 100/ 100. Of note is that two SNPs showing genetic interaction in this model were not significantly associated with an increased risk of IPA infection in the univariate analysis (CCR2 rs3918358 and Dectin-2 rs7134303 ). The best two-locus model consisted of the Dectin-1 rs3901533 and DC-SIGN rs4804800 SNPs, two variants that showed also association in the single-locus analysis. This model had a testing accuracy of 0.6409 and a cross-validation consistency of 76/100. This model was not any more significant after 1.000-fold permutation testing. However, the entropy based information gain calculated for this pair of SNPs indicated strong synergy, which may be interpreted as the two SNPs acting together to increase the risk of IPA infection. The best three-locus model included the CCL2 rs4586 , Dectin-1 rs3901533 and Dectin-2 rs7134303 SNPs. In this model, testing accuracy raised to 0.7085 (permutation p = 0.025) whereas the cross-validation consistency was of 68/100. Figure 3 illustrates an interaction dendogram that summarizes the estimates of interactions.