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The following is a summary of “rs6967330 minor allele in CDHR3 is a significant risk factor for severe acute exacerbations in CRS,” published in the October 2024 issue of Allergy and Immunology by Palumbo et al.
Acute exacerbations of chronic rhinosinusitis (AECRS) are often triggered by rhinovirus (RV) infections. The risk factors for AECRS are poorly understood.
Researchers conducted a retrospective study to assess whether carriers of the rs6967330 (AA/AG) minor allele in Cadherin-related family member 3 (CDHR3) have an increased risk for RV infections in AECRS and to identify genotype-dependent host responses in nasal airway liquid interface (ALI) cultures.
They conducted a year-long study of adults with chronic rhinosinusitis (CRS) by rs6967330 genotype (AA/AG, n=16; GG, n=38). Subjects were contacted biweekly, and clinical data were collected upon reporting AECRS. Air-liquid interface (ALI) cultures from adults with CRS (AG/AA, n=19; GG, n=19) were challenged with RV-A and C. They measured viral copy numbers at 4- and 48-hours post-infection and assessed RNA transcriptomes and cytokines at 48 hours.
The results showed that subjects with the minor allele had higher rates of rhinovirus (RV) and bacterial infections than those with the major allele. ALI cultures with the minor allele exhibited higher viral copy numbers of RV-A and RV-C after 48 hours. Differentially expressed genes (DEG) indicated an upregulation of IL-10 and IL-4/13 pathways and a downregulation of toll-like receptor (TLR) pathways in minor allele cultures after RV-A and RV-C infection. Unsupervised hierarchical analysis suggested that allergic rhinitis had an additive effect on this response.
The study concluded that the rs6967330 minor allele was linked to increased RV-A and RV-C replication and downregulation of TLR-mediated responses during rhinovirus infection.
Source: jacionline.org/article/S0091-6749(24)01028-5/abstract
