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

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, = 36) participants developed only an EPR, while persistent congestion (PC, = 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 , and had significantly different allele frequencies ( < 0.10) between PC and AC participants. PC participants had increased minor allele content ( = 0.009) in the 25 SNPs compared to AC participants. Two SNPs in were associated with gene expression differences (FDR < 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.