Asthma impacts 25 million Americans. Having an asthmatic mother is a significant risk factor, and a new study may explain why.
Individuals with asthma who had asthmatic mothers show striking epigenetic differences in their airway cells compared to patients whose mothers never had asthma, according to a team of researchers from the University of Chicago.
The findings were reported in the Proceedings of the National Academy of Sciences on June 6.
Carole Ober, PhD, and her research team have spent years looking into the genetic and epigenetic effects that play a role in asthma development.
Alterations in gene expression that are not caused by changes or mutations in the DNA sequence are referred to as epigenetics. Instead, tiny chemical structures such as methyl groups can be attached to DNA to toggle gene activity on or off.
Many environmental factors, including the in-utero environment, are known to influence DNA methylation patterns.
When comparing asthmatic adults with asthmatic moms to those whose mothers did not have asthma, the researchers discovered distinct DNA methylation patterns in epithelial cells of the lower airways.
“The methylation patterns in those with asthmatic mothers were tied to reduced expression of genes in immune-related pathways,” says first author Kevin Magnaye.
These immune-related pathways, which include pathways linked to defective immunological responses to viruses and bacteria, are linked to impaired T cell signaling, a kind of adaptive immune cell important in battling infections. In terms of clinical manifestations, there is a severe form of asthma known as type 2-low asthma, which is characterized by a lack of response to traditional corticosteroid therapies, which decrease inflammatory processes.
Ober, the Blum-Riese Distinguished Service Professor of Human Genetics, adds, “This subtype of asthma is particularly difficult to treat. “Our results suggest that an underlying cause is due to impaired immune responses, potentially explaining lack of therapeutic response to corticosteroids and suggesting alternative pathways to target as therapies for this group of patients .”
One of the most noteworthy aspects of this study is that it was carried out in a diverse population. Patients from the UChicago Medicine asthma clinics took part in the study. Many dwell on the South Side, which has a particularly high asthma rate.
“Having representation of diverse ancestry and sociocultural factors is important in research, as it tells us these findings hold true across various populations,” Magnaye adds. There are large differences in asthma rates, emphasizing the importance of diversity in asthma research.
The research was done with cells from adult patients, but the results were excitingly repeated in airway epithelial cells from a separate sample of youngsters. Researchers believe that the asthmatic patients’ epigenetic changes happened during pregnancy, and that their exposure to the asthmatic mother’s in-utero environment impacted their chances of developing asthma later in life.
“The fact that these results were replicated in a separate cohort of children supports the notion that these modifications are present long before adulthood,” Ober says.
To determine the chronology of these changes and their implications on asthma, more research is needed. Ober’s team is currently conducting a longterm research in neonates to investigate these temporal impacts further.
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