Association of candidate genes with FeNO in asthma: preliminary results from the Gene Environment Interactions in Respiratory Diseases (GEIRD) study

The present candidate gene analysis is aimed at identifying the genetic polymorphisms associated with FeNO in adult subjects with asthma. We evaluated 227 subjects with asthma (age: 20-66 years; female: 49.3%; current smoking: 23.3%; past smoking: 31.7%; atopy: 76.6%), who had been identified from the general population in Verona (Italy) in the clinical stage (2008-2010) of a multi-centre (multi)case-control study (GEIRD). All subjects in our sample had not used controller drugs in the previous 3 months. A panel of 210 tag-SNPs, which are representative of 50 candidate genes with a previous indication of a possible association with asthma/COPD/rhinitis, was genotyped by a custom GoldenGate Genotyping Assay. The association with log-transformed FeNO (at an expiratory flow rate of 50 mL/s) was tested separately for each SNP (classified according to the additive, dominant or recessive genetic model) by a linear regression model with robust standard errors, adjusting for sex and smoking habits. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR). SNP rs1610696 in Human Leukocyte Antigen-G (HLA-G) and SNP rs174579 in Fatty Acid Desaturase 2 (FADS2) gene regions were significantly associated with FeNO. These preliminary results suggest that HLA-G and FADS2, or genes in linkage disequilibrium, play a role in inflammation among adult asthmatics.