Novel genetic variants influencing eosinophil-derived protein levels in asthma families
Published: June 4, 2022
Asthma is one of the most common chronic diseases affecting more than 260 million people worldwide. The genetic component of asthma is substantial, but many of the genetic factors are yet to be discovered. Eosinophil cells play a key role in the asthma allergic response by releasing cytotoxic enzymes such as eosinophil cationic protein and eosinophil-derived neurotoxin that damage the airway and the lung tissue. The study of such biological phenotypes involved in the mechanisms underlying asthma can help in understanding the complex genetic architecture of asthma.
In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), Vernet et al. aimed at identifying the genetic factors influencing eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) levels measured in families recruited through subjects with asthma. For this purpose, the authors examined the relationship between genome-wide genetic variants and the levels of ECP and EDN in 1,018 subjects from the French EGEA study (Epidemiology study on the Genetics and Environment on Asthma, https://egeanet.vjf.inserm.fr/). Then, EGEA findings were followed-up in 153 subjects belonging to French Canadian families from the SLSJ study (Saguenay-Lac-Saint-Jean), and the results of these two studies were combined through meta-analysis.
By using sophisticated analyses together with gene expression and DNA methylation data, which included data from a unique resource of eosinophils, the researchers identified six genes involved in the regulation of ECP and EDN levels: RNASE2 and RNASE3 which encode EDN and ECP respectively; JAK1 a transcription factor with a key role in the immune response and a potential therapeutic target for eosinophilic asthma; ARHGAP25 involved in the migration of immune cells to inflammatory sites; NDUFA4 encoding a component of the mitochondrial respiratory chain and involved in cellular response to stress; and CTSL involved in immune response, extra-cellular remodeling and allergic inflammation.
This study highlights the importance of analyzing enzymes produced by eosinophils in order to identify novel genes that play a role in allergic response and inflammation, thus offering potential therapeutic targets for asthma.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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