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

Area of Science:

• Immunology
• Genetics
• Pharmacology

Background:

• Allergic rhinitis (AR) involves early-phase (EPR) and late-phase responses (LPR).
• Cholinergic synapse pathway genes are implicated in late asthmatic responses.
• Nasal congestion is a key symptom of the LPR in AR.

Purpose of the Study:

• Investigate polymorphisms in cholinergic synapse pathway genes in relation to the LPR of AR.
• Sub-phenotype AR participants based on nasal congestion severity and duration.
• Explore the association between genetic variations and gene expression in AR subtypes.

Main Methods:

• Allergen exposure in a controlled Environmental Exposure Unit for 20 healthy and 74 AR participants.
• Sub-phenotyping AR participants into acute congestion (AC) and persistent congestion (PC) groups.
• Genotyping and gene expression assays on blood samples to analyze SNPs in cholinergic pathway genes.

Main Results:

• Significant differences in allele frequencies of 25 SNPs across seven genes (ADCY3, AKT3, CACNA1S, CHRM3, CHRNB2, GNG4, KCNQ4) between PC and AC groups (P < 0.10).
• PC participants exhibited increased minor allele content in these 25 SNPs (P = 0.009).
• Two SNPs in AKT3 were associated with altered gene expression in PC participants (FDR < 0.01).

Conclusions:

• Identified an association between LPR in AR and polymorphisms in cholinergic synapse pathway genes.
• Developed a novel method for sub-phenotyping AR using self-reported nasal congestion scores.
• Suggests a genetic basis for persistent symptoms in AR, potentially influencing LPR development.