Background: Asthma is a complex chronic disease that involves the interaction among multiple genetic and non-genetic factors, and that is characterized by various phenotypes. In particular, airway eosinophilic inflammation might be aggravated by the coexistence of airway neutrophilia to confer a severe mixed asthma phenotype.

Aim: To assess the association between SNPs in candidate genes and mixed granulocytic asthma (MGA) in adult subjects with asthma.

Methods: In the Gene Environment Interactions in Respiratory Diseases survey (GEIRD, 2008-2010), 220 adult subjects with asthma (aged 21-66 yrs) were identified from the general population (Verona, Italy) and were classified as having MGA [blood eosinophils (EOS) ?250 cells/mm-3 and blood neutrophils (NEU) ?5000 cells/mm-3; n=30] or paucigranulocytic asthma (PA) [blood EOS <250 cells/mm-3 and blood NEU <5000 cells/mm-3; n=190]. Ninety-six SNPs tagging 24 candidate genes with known immune-function were selected for the present analysis. The association between each SNP (additive genetic model; reference genotype: homozygous with highest allele frequency) and the outcome (MGA vs PA) was assessed by using logistic regression models, with age and sex as covariates. The p-values were adjusted to control for the false discovery rate using the Simes multiple testing procedure.

Results: SNP rs1063320 (genotype CC: 65 subjects; CG: 102 subjects; GG: 53 subjects) in human leukocyte antigen G (HLA-G) gene was significantly associated with MGA compared to PA (uncorrected p-value: 0.0005; adjusted p-value: 0.0496).

Conclusion: After adjusting for multiple testing, a SNP in HLA-G gene is significantly associated with MGA in adult subjects with asthma.