Researchers from the Genomics and Health group of the University of La Laguna have published an article in the international journal Pulmonology, in collaboration with the Hospital Universitario de Canarias and the Hospital General de la Palma, in which the association between genetic changes and asthma attacks was established for the first time.
Throughout the last decades, scientific evidence has shown that certain changes in the DNA sequence, which specifically affect a gene known as SERPINA1, are involved in the development of certain serious respiratory diseases. However, its role in the development of asthma, and especially in worsening episodes of this disease, was still in question until this recent study.
Asthma is a chronic respiratory disease characterized by inflammation and reversible obstruction of the airways. Surprisingly, the Canary Islands have one of the highest prevalences in Europe and the highest in the entire Spanish territory, since it is currently estimated that around 17% of Canary Islands suffer from it. In addition to the enormous impact on the quality of life of patients, asthma generates great economic pressure on health systems, due both to hospital admissions, as well as the use of expensive drug therapies, visits to specialists and emergency care.
Although their symptoms can usually be controlled with appropriate treatment, patients with asthma can experience severe episodic flare-ups, known as exacerbations, which greatly increase the risk of death from asthma. Therefore, the prevention of these “asthma attacks” represents an essential pillar in the management of the disease and, to achieve this, it is necessary to detect biomarkers that identify those patients at high risk of suffering these exacerbations. In fact, this line of research is currently considered a key pillar in the emerging field of personalized medicine.
In this scientific article, researchers have shown that a decrease in the blood concentration of the protein encoded by the SERPINA1 gene, known as Alpha-1 antitrypsin (AAT), is associated with an increased risk of asthmatic exacerbations. The AAT protein is the second most abundant protein in blood serum and exerts its main function in the lungs, controlling the degradation of lung tissue during inflammatory processes. Therefore, it is not surprising that high levels of AAT in the blood exert a protective effect on the development of asthma exacerbations, while low levels are associated with an increased risk of suffering “asthma attacks”.
This relationship between AAT blood levels and asthma exacerbations has been demonstrated for the first time in this work, using a sample of the asthmatic population recruited over several years on the island of La Palma. In addition, the research team has provided evidence of the association between a specific variant of the SERPINA1 gene, known as Pi*Z, with asthma exacerbations. This genetic change, widely studied for decades by the scientific community, has been related to a great reduction of the AAT protein in the blood, and is considered the main cause of the genetic disorder known as Alpha-1 antitrypsin deficiency (AATD).
Notably, the PI*Z variant reaches its highest frequency among European populations, including the Canary Islands, and this study has demonstrated its association with asthma exacerbations in asthmatic patients from La Palma. Furthermore, this relationship has been validated in an independent sample of patients with Canarian ancestry, but not in asthmatics from other Spanish populations, which could be related to the high incidence of this disease on the islands.
The Canarian populations present a recent mix between North African, European and Sub-Saharan ancestry, with variable ancestry for each specific island. Although a relationship between genetic ancestry and asthma has not been shown when individuals from the Canary Islands have been analyzed as a whole, to date no studies based on specific island populations have been addressed, as has been done in this work. These results point to the need to treat each island as an independent population, taking into account its genetic characteristics, which represents a new workhorse for the scientific community.
This work highlights the usefulness of personalized medicine to solve the great challenges in the field of health, something especially relevant for the Canarian population, taking into account their unique genetic characteristics. In fact, personalized medicine has already shown that certain drugs have different levels of efficacy and safety depending on their prescription in specific populations.
In this sense, in the near future it could be very useful to consider the measurement of Alpha-1 antitrypsin levels in asthmatic patients, something easily achievable in any clinical laboratory from a routine blood test, as well as to characterize the causative genetic variants. of the AATD in these patients, especially when there are episodes of previous exacerbations in time. In this way, patients carrying deficient variants for the SERPINA1 gene could be detected, and a more exhaustive control of the risk of suffering new exacerbations could be carried out.
Finally, this study opens a new debate for the scientific community, since it raises the possibility of using the only therapy currently prescribed for the treatment of severe AATD (known as AAT replacement therapy), as a possible potential treatment to reduce the severe exacerbations of asthma, especially in canary patients who do not respond to other treatments.
