The following is a summary of “Identification of novel genes influencing eosinophil-specific protein levels in asthma families” published in the November, 2022 issue of Allergy and clinical immunology by Vernet, et al.


By producing cytotoxic chemicals that cause epithelial damage, such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), eosinophils play a crucial part in the allergic asthmatic response. Researchers looked for genetic variations affecting ECP and EDN levels in families with confirmed asthma.

Using 153 participants from the Saguenay-Lac-Saint-Jean study as the follow-up, they conducted univariate and bivariate genome-wide association analyses of ECP and EDN levels in 1,018 participants from the EGEA trial. The results of these 2 investigations were then integrated by meta-analysis. They next used Bayesian statistical fine mapping, quantitative trait locus analysis, and functional annotation studies to pinpoint the candidate genes and genetic variations most likely to be functional.

We discovered 5 genome-wide significant loci (P < 5 × 10-8) that included 7 different signals related to ECP and/or EDN levels. The precision mapping and functional search focused on 4 additional genes that control the amounts of ECP and EDN in addition to RNASE2 and RNASE3 (14q11), which encode EDN and ECP, respectively. These 4 genes were CTSL (9q22), which is involved in immune response, extracellular remodeling, and allergic inflammation; JAK1 (1p31), a transcription factor that is important for the immune response and may serve as a therapeutic target for eosinophilic asthma; ARHGAP25 (2p13), which is involved in leukocyte recruitment to inflammatory sites; NDUFA4 (7p21), which encodes a component of the mitochondrial respiratory chain and is involved in the cellular stress response;

Analysis of specific phenotypes eosinophils produce enabled the discovery of genes that are important in allergic response and inflammation and provides prospective treatment targets for asthma.

Reference: jacionline.org/article/S0091-6749(22)00762-X/fulltext