The following is a summary of “Aspirin-exacerbated respiratory disease is associated with variants in filaggrin, epithelial integrity, and cellular interactions,” published in the MAY 2024 issue of Allergy & Immunology by Jerschow, et al.

Previous research has indicated that up to 6% of patients with aspirin-exacerbated respiratory disease (AERD) have a family history of the condition, suggesting a potential genetic link. However, studies using whole exome sequencing (WES) to explore these genetic associations are currently lacking. For a study, researchers sought to investigate whether WES can identify pathogenic variants associated with AERD.

Patients diagnosed with AERD, characterized by nasal polyps and asthma, were selected for the study. Whole exome sequencing was conducted using the Illumina sequencing platform. The patients’ phenotypes were defined using Human Phenotype Ontology terms. Exomiser annotated, filtered, and prioritized potential disease-causing genetic variants.

Among the 39 patients with AERD, 41% reported a family history of asthma, and 5% reported a family history of AERD. Pathogenic variants in the filaggrin gene (FLG) were identified in 2 patients (5%). Additionally, 16 patients (41%) had variants in genes related to epithelial integrity and cellular interactions, although these variants were not previously recognized as pathogenic. These genes included desmoglein 3 (DSG3), dynein axonemal heavy chain 9 (DNAH9), collagen type VII alpha 1 chain (COL7A1), collagen type XVII alpha 1 chain (COL17A1), chromodomain helicase DNA binding protein-7 (CHD7), TSC complex subunit 2/tuberous sclerosis-2 protein (TSC2), P-selectin (SELP), and platelet-derived growth factor receptor-alpha (PDGFRA).

Whole exome sequencing identified a monogenic susceptibility to AERD in 5% of patients due to pathogenic variants in the FLG gene. Other variants in genes associated with epithelial integrity and cellular interactions were identified, which may further elucidate the genetic factors contributing to AERD.

Source: jaci-global.org/article/S2772-8293(24)00001-8/fulltext