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Investigating molecular and genetic differences in allergic rhinitis phenotypes Samra, Simranjit


Allergic rhinitis (AR) is a heterogeneous disorder that is associated with inflammation of the upper airways. The prevalence of AR has increased rapidly in recent years, and currently affects 10 - 40% of the global population. Common examples of symptoms experienced after allergen exposure include nasal congestion, rhinorrhea, sneezing, and nasal itching. Additional symptoms include conjunctivitis and exacerbation of comorbid asthma. AR is characterized by an early phase response (EPR) and, in some individuals, a subsequent late-phase response (LPR). The induction of allergic responses can be studied using controlled allergen challenge facilities (CACF). Multiple CACFs have identified three response phenotypes in AR: early responders, protracted early responders, and dual responders. Molecular and genetic differences between AR phenotypes have not been well investigated. In order to identify molecular differences between phenotypes, we used baseline peripheral blood collected from individuals with AR. Blood samples from discovery and validation cohorts were profiled for biomarker candidates using a custom gene expression assay. Using univariate and multivariate analyses, we were unable to identify and validate a clear discriminatory signal between AR phenotypes. Next, we investigated the relationship between single nucleotide polymorphisms (SNPs) in cholinergic synapse pathway genes and the development of the LPR. We specifically looked at the cholinergic synapse pathway because polymorphisms in these genes have previously been associated with late asthmatic responses. Participants were split into two categories based on late-onset congestion, which is the predominant nasal symptom experienced during the LPR: low congestion (LC) and high congestion (HC). Allele frequencies of 25 SNPs located in cholinergic synapse pathway genes (ADCY3, AKT3, CACNA1S, CHRM3, CHRNB2, GNG4, and KCNQ4), were found to be significantly different between HC and LC subgroups. Additionally, we identified that the minor allele content of the HC subgroup was significantly higher than that of the LC subgroup. The cholinergic system may be a potential therapeutic target for the LPR.

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