The association among inflammation-related genes, fractional exhaled nitric oxide (FeNO), and symptom severity in adult asthma: a structural equation model (SEM).

Background. Airway inflammation is a key component of asthma that depends on the interplay of multiple genes. However, the association between health outcomes and genetic factors is usually evaluated by testing each candidate gene variant individually. Aim. To simultaneously assess the association of symptom severity with tag-SNPs located in inflammation-related genes and the FeNO level. Methods. In Verona (Italy), 327 asthmatics (aged 20-64) were identified from the general population in the GEIRD study (2008/2010). Individuals underwent a clinical interview, blood sampling for genotyping, and the measurement of FeNO (200 ml/s). SNPs in the CHI3L1, RAD50/IL4/IL5/IL13, IL33, and MS4A2 gene regions were genotyped by a custom GoldenGate Genotyping Assay. A symptom severity score (SSS) was computed by a multiple correspondence analysis on the basis of asthma-like symptoms, asthma attacks and hospitalization in the past year. The association of the SSS with SNPs and FeNO was assessed by a SEM. SNPs were summarised by a latent variable; atopy, gender, smoking habits and ICS use in the past year were considered as potential confounders. Results. The SEM is described in figure 1. Conclusions. This preliminary analysis suggests that inflammation-related genes could have a direct effect (not mediated by FeNO and atopy) on symptom severity in adult asthmatics