Published online: October 24, 2018
Although over 25 million individuals in the U.S. have asthma, African Americans and other minority groups suffer from more severe asthma and experience more frequent attacks. Inhaled corticosteroids are considered to be the most effective treatment for improving asthma control and preventing attacks. However, currently there only a few markers available for predicting whether a person with asthma will respond to controller treatment, and even less information is available for understudied minority populations.
In an article recently published in The Journal of Allergy & Clinical Immunology (JACI), Levin and colleagues from Henry Ford Hospital presented results from their study to uncover new predictors of asthma controller medication response. The investigators used genetic data collected from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE), an ongoing study of individuals from southeast Michigan and metropolitan Detroit funded by the U.S. National Institutes of Health. The scientists first scanned the genome of African American study participants from the SAPPHIRE cohort for genetic variants that were associated with improved asthma control while receiving inhaled corticosteroid treatment. Collaborating with scientists from the University of California San Francisco, the investigators then reassessed whether their genetic findings were associated with severe asthma attacks in different groups of asthmatics. In total, 1,610 African Americans, 1,461 Latinos, and 98 non-Hispanic white individuals were studied.
The researchers identified a strongly significant association for inhaled corticosteroid response among individuals who carried a “C” genetic variant on chromosome 14 (at marker rs3827907). This variant was associated with both improved asthma control and less frequent asthma attacks while using inhaled corticosteroid medication. Follow-up studies by the researchers demonstrated that carriers of the variant had lower gene expression of RNASE2, the gene responsible for producing a protein called eosinophil-derived neurotoxin (EDN). Eosinophils are a type of white blood cell often implicated in allergic and asthma-related inflammation, and EDN is among the proteins released by eosinophils when they are activated. As a result, the investigators re-analyzed their data to examine whether “C” variant carriers with asthma responded differently to inhaled corticosteroid treatment when eosinophilic inflammation was also present. In short, they observed that “C” variant carriers with evidence of eosinophilic inflammation (high blood eosinophil levels) were the group who appeared to be the most responsive to inhaled corticosteroid medication.
This is the first genetic study to use a predominantly non-white study population to identify new biomarkers for predicting response to asthma controller medication. The study suggests that combining evidence from blood (for eosinophilic inflammation) and genetic data may provide a future path for identifying individuals most likely to respond to asthma treatment.
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.
18-00782R1, Integrative approach identifies corticosteroid response variant in diverse populations with asthma