Association of Host CDHR3 rs6967330 Genotype with Rhinovirus Infections in Children from 1997-2018

Document Type

Conference Proceeding

Publication Date

2-1-2025

Publication Title

J Allergy Clin Immunol

Abstract

Rationale: The single-nucleotide polymorphism rs6967330 in the rhinovirus C (RV-C) receptor cadherin related family member 3 (CDHR3) gene is associated with increased CDHR3 expression on airway epithelial cells and risk of asthma in children. We hypothesize that RV-C types rarely found during childhood infection are more common in hosts with AA/AG risk CDHR3 genotypes compared to GG homozygotes due to increased receptor density mediating greater viral binding and entry. Methods: We pooled multicenter data from 6 cohorts with RV typing from partially sequenced nasal samples from 1997-2018 (n=2095 patients age 0-18, 6325 samples, 5515 with genotype). We compared the proportions of infections in AA/AG to GG participants for each RV type and performed linear regression analysis grouped by species (RV-A, RV-B, and RV-C). Pearson correlations were calculated to evaluate linear relationship. Results: Children with AA/AG genotypes had higher rates of RV-C infections compared to children with GG genotype (slope=1.17). This was not true for RV-A or RV-B infections (slope=0.791 and 0.864, respectively). Pearson correlations revealed similarly strong linear relationship for all 3 RV species (RV-A, RV-B, and RV-C) with overlapping 95% confidence intervals (r=0.86 [0.79,0.91], r=0.90 [0.80,0.95], and r=0.89 [0.82,0.93], respectively). Conclusions: We demonstrated that children carrying the rs6967330 risk allele (A) have more RV-C infections within our large multicenter population. Contrary to our hypothesis, the CDHR3 risk genotypes AA/AG increased infections with all RV-C types and not just the less common viruses. These findings suggest that increased receptor density on airway epithelial cells generally increases susceptibility to RV-C infection.

Volume

155

Issue

2

First Page

AB296

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