SNPs inFAM13AandIL2RBgenes are associated with FeNO in adult subjects with asthma.

Nitric oxide has different roles in asthma as both an endogenous modulator of airway function and a pro-inflammatory mediator. Fractional exhaled nitric oxide (FeNO) is a reliable, quantitative, non-invasive, simple, and safe biomarker for assessing airways inflammation in asthma. Previous genome-wide and genetic association studies have shown that different genes and single nucleotide polymorphisms (SNPs) are linked to FeNO. We aimed at identifying SNPs in candidate genes or gene regions that are associated with FeNO in asthma. We evaluated 264 asthma cases (median age 42.8 years, female 47.7%) who had been identified in the general adult population within the Gene Environment Interactions in Respiratory Diseases survey in Verona (Italy; 2008-2010). Two hundred and twenty-one tag-SNPs, which are representative of 50 candidate genes, were genotyped by a custom GoldenGate Genotyping Assay. A two-step association analysis was performed without assuming ana priorigenetic model: step (1) a machine learning technique [gradient boosting machine (GBM)] was used to select the 15 SNPs with the highest variable importance measure; step (2) the GBM-selected SNPs were jointly tested in a linear regression model with natural log-transformed FeNO as the normally distributed outcome and with age, sex, and the SNPs as covariates. We replicated our results within an independent sample of 296 patients from the European Community Respiratory Health Survey III. We found that SNP rs987314 in family with sequence similarity 13 member A (FAM13A) and SNP rs3218258 in interleukin 2 receptor subunit beta (IL2RB) gene regions are significantly associated with FeNO in adult subjects with asthma. These genes are involved in different mechanisms that affect smooth muscle constriction and endothelial barrier function responses (FAM13A), or in immune response processes (IL2RB). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation.

IL18 Gene Polymorphism Is Associated with Total IgE in Adult Subjects with Asthma.

The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008-2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998-2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes.