Gene Expression Changes in airway cells mediated genetic risk in asthma

Gene Expression Changes in airway cells mediated genetic risk in asthma ...

A substantial amount of genetic risk for asthma is likely to be mediated by altered gene expression within the airway epithelium. This is the conclusion of a National Jewish Health-led study to identify genetic variants that cause asthma by altering the function of airway cells. The team study has been published today in the journalNature Communications.

This research will help us identify feasible interventions to combat asthma, to stop mucus hypersecretion or type 2 airway inflammation, an allergic reaction that can exacerbate asthma, according toMax A. Seibold, a researcher at the National Jewish Health Center for Genes, Environment, and Health. One of the limitations of human existence is mucus, which plays a role in so many health conditions, from the common cold, to COVID, to chronic lung diseases, and is better equipped to develop effective therapies.

The first step in a TWAS study for childhood and adult onset asthma is to develop models that can imply how a person''s genes will function in a particular tissue, based solely on their genetic profile. Dr. Seibold and his colleagues re-analyzed nasal airway samples and genetic data from a group of 700 people in Puerto Rico who either were in good health or had asthma. These experiments were then used to develop airway tissue.

These experiments were then applied to biomedical data from over 300,000 participants in the UK Biobank study, a large-scale biomedical database and research resource. This allowed them to discover whether the genetically altered function of airway genes is associated with asthma risk. The study data found over a third of identified asthma risk factors may result in their risk by altering the cells that line the airways (i.e. airway epithelium).

Genetic changes in a gene that forms the structure of mucus (MUC5AC) and another gene (FOXA3) that regulates the production of mucus secretory cells have been discovered. This is one of the first instances in history that anyone has found genetic modifications that have a bearing on asthma risk through altered mucus secretory functions. A study also revealed that some of the key genes in the type 2 inflammatory pathway have genetic modifications that increase their levels of expression in the airway, increasing asthma risk.

This study was funded primarily by the National Heart, Lung, and Blood Institute (NHLBI). The Institute is an international leader in research, training, and educational programs that promote the prevention and treatment of heart, lung, and blood illnesses and improve the health of all individuals, thus allowing them to live longer and longer lifelong. The NHLBI is one of the national hospitals in the United States of Health.

This study demonstrates how obtaining additional information on gene expression datasets from participants in genome-wide association studies can clarify their biological capabilities. It also demonstrates that some genes may be expressed differently in different tissues, according to James P. Kiley, PhD, who is the director of the NHLBIs Division of Lung Diseases. This approach enables us to get more advanced with personalized medication programs for asthma and other common diseases.

Asthma is a major health problem in the United States. According to the Centers for Disease Control, 26.5 million people, or one in 13 people, are living with the condition.

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