Interactions between candidate gene polymorphisms and air pollutants on asthma severity in adults

<bold>Background:</bold> Asthma is a complex chronic disease, which involves the interplay of genetic, environmental and lifestyle factors. <bold>Aim:</bold> To identify SNPs in 50 candidate genes that modify the relationship between residential air pollutants and asthma severity in adults from the general Italian population. <bold>Methods:</bold> We considered 198 adults with current asthma (aged 21-66 years; female 46.0%), who had been identified in Verona as part of the Gene Environment Interactions in Respiratory Diseases (GEIRD; 2008-10) survey. We carried out a genetic association analysis using the continuous Symptom frequency and anti-asthmatic Treatment intensity Score (STS) as the outcome. The interaction between each SNP (166; classified according to the additive genetic model) and each pollutant (NO₂, O₃, PM_2.5, PM₁₀; average concentration in 2013-15) on zero-skewness Box-Cox transformed STS score was assessed using a reparametrized linear regression model, adjusting for age and sex. The difference in slope was tested for each of the three pairs of genotypes and the lowest p-value was corrected to control the FDR using Simes' multiple testing procedure. <bold>Results:</bold> We identified an interaction between SNP rs1553318 (number of subjects by genotype; GG:58; CG:99; CC:38) in Hepatitis A Virus Cellular Receptor 1 (HAVCR1) gene and NO₂ on asthma severity (uncorrected p-value=0.0002; FDR-corrected p-value=0.030). <bold>Conclusion:</bold> HAVCR1 gene encodes a membrane receptor that acts as a regulator of T-cell proliferation and Th1/Th2 differentiation, which are crucial processes in the development of inflammatory responses. Variants in HAVCR1 gene may moderate the effects of environmental exposure on asthma and other allergic diseases.