AUTHOR=Samra Simranjit K. , Rajasekaran Ashwini , Sandford Andrew J. , Ellis Anne K. , Tebbutt Scott J. 

TITLE=Cholinergic Synapse Pathway Gene Polymorphisms Associated With Late-Phase Responses in Allergic Rhinitis

JOURNAL=Frontiers in Allergy

VOLUME=2

YEAR=2021

URL=https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2021.724328

DOI=10.3389/falgy.2021.724328

ISSN=2673-6101

ABSTRACT=<p>Allergic rhinitis (AR) is characterized by an early-phase response (EPR), and in a subgroup of individuals, a late-phase response (LPR). We sought to investigate polymorphisms in cholinergic synapse pathway genes, previously associated with late-asthmatic responses, in the LPR. Twenty healthy participants and 74 participants with AR underwent allergen exposure using the Environmental Exposure Unit. Allergic participants were sub-phenotyped using self-reported nasal congestion scores; congestion is the predominant symptom experienced during the LPR. Acute congestion (AC, <italic>n</italic> = 36) participants developed only an EPR, while persistent congestion (PC, <italic>n</italic> = 38) participants developed both allergic responses. We interrogated blood samples collected before allergen exposure with genotyping and gene expression assays. Twenty-five SNPs located in <italic>ADCY3, AKT3, CACNA1S, CHRM3, CHRNB2, GNG4</italic>, and <italic>KCNQ4</italic> had significantly different allele frequencies (<italic>P</italic> &lt; 0.10) between PC and AC participants. PC participants had increased minor allele content (<italic>P</italic> = 0.009) in the 25 SNPs compared to AC participants. Two SNPs in <italic>AKT3</italic> were associated with gene expression differences (FDR &lt; 0.01) in PC participants. This study identified an association between the LPR and polymorphisms in the cholinergic synapse pathway genes, and developed a novel method to sub-phenotype AR using self-reported nasal congestion scores.</p>