Asthma: More Than Just Genetics

Countless parents go to the pediatrician each year when their toddler starts wheezing, worried that their child has asthma. But less than half of these children actually go on to develop asthma.¹

Differences in people’s DNA may play a role, since certain racial/ethnic groups, such as Puerto Ricans, are much more likely to have severe asthma. However, Mexican Americans—who have an ethnic background similar to that of Puerto Ricans—have much lower rates of the condition.^2, ³

Scientists do not understand why asthma affects Puerto Ricans and other populations more than it affects Mexican Americans, although this difference suggests that a person’s environment may play a greater role in asthma than genetics do. An NIMHD-supported study found an important way in which the environment might affect gene expression in asthma. The researchers found unique marks on the DNA of Puerto Rican children and teens with asthma. The pattern of these marks could help doctors predict who will develop the illness.

These DNA marks do not change a person’s underlying DNA sequence, but they determine whether a gene is active; if a gene is not active, it’s similar to information that is in code and cannot be read. All kinds of factors, such as age, environment, and diet, can affect the DNA marks. This concept, called epigenetics, helps explain why one person may get a disease while a close relative with similar DNA does not. Researchers at the University of Pittsburgh Medical Center (UPMC) Children’s Hospital of Pittsburgh wanted to know whether these DNA marks could clarify why some children develop asthma.

Studying DNA Marks in Asthma

The study looked at nose tissue samples from nearly 500 children and teens living in Puerto Rico, including 169 children with allergic asthma. This is the most common type of asthma, in which allergens, such as pollen, dust, and pet dander, cause tightening of the airway, leading to wheezing and shortness of breath. The research team identified all the DNA marks across each child’s entire DNA code and compared them with the marks in children who do not have asthma.

The principal investigator of this research effort, Juan C. Celedón, M.D., Dr.P.H., has seen many children with asthma as a physician and now as the chief of service in the Division of Pediatric Pulmonary Medicine at UPMC Children’s Hospital of Pittsburgh. He also shares a connection with the study population, saying, “I am quite passionate about health disparities research because of my Latino background.”

Dr. Celedón and his Pittsburgh colleagues, including Erick Forno, M.D., M.P.H., collaborated with researchers in Puerto Rico, led by Glorisa Canino, Ph.D., and Edna Acosta-Pérez, Ph.D., M.Sc., to recruit the study participants and collect the tissue samples.

Finding DNA Marks for Predicting Asthma

The researchers found that children and teens with allergic asthma have a very different pattern of DNA marks than children who do not have asthma do.⁴ The findings, which were also supported by the National Heart, Lung, and Blood Institute (NHLBI), were published in the April issue of The Lancet Respiratory Medicine.

In fact, the team found thousands of places where the DNA marks were different. The location of these variations could affect a person’s natural immune defense—in this case, limiting the ability to filter irritating particles breathed in through the nose. However, looking at all of these marks in every child who wheezes and comes in for an asthma test would be overwhelming. Dr. Celedón and his team narrowed the list down to about 30 marks, finding that these marks could help predict asthma in diverse populations, including African Americans and Whites, not just Puerto Ricans. With this information, scientists may continue studying small children and see what patterns are linked to developing asthma.

To confirm their findings, Dr. Celedón’s team is planning an ambitious study that will follow babies until adulthood. The researchers will collect data on DNA marks at the beginning of the study and over time to develop a way to predict who will develop asthma, who will have asthma attacks, and which treatments will work for which patients.

Looking at How Stress Alters DNA Marks

Dr. Celedón says that his team is particularly interested in how stress affects DNA marks. Currently, the team is investigating whether exposure to violence and long-term stress lead to DNA changes that affect how well asthma treatment works for people. The study will include 300 Puerto Rican children who receive inhaled steroids to treat asthma. By examining samples of nasal tissue, the team hopes to find ways to predict whether treatment will work in certain individuals. The researchers hope to determine whether long-term stress can lower a person’s response to steroids. The team has already found that DNA changes in a gene linked with post-traumatic stress disorder in adults and anxiety disorder in children is also associated with asthma in Puerto Rican teens.⁵ “This is just one example involving one gene, but it gave us reason to believe that other genes could be implicated,” says Dr. Celedón.

Unraveling the Hispanic Health Paradox

Underlying the team’s research is a core goal: to understand a phenomenon known as the Hispanic health paradox. This term often refers to the relatively good health of Latinos within the United States, despite what their lower levels of socioeconomic status might predict. However, the paradox also describes major differences in health status within Latino subgroups, such as the large variance in asthma rates between Puerto Ricans and Mexican Americans. The team members hope their work will ultimately help mitigate these disparities.

Dr. Celedón also pursues this goal through involvement in other projects, such as the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), and he serves as a mentor to aspiring minority health researchers helping to advance the field.

References

van Aalderen, W. M. (2012). Childhood asthma: diagnosis and treatment. Scientifica, 2012, 674204. doi:10.6064/2012/674204
Moorman, J. E., Akinbami, L. J., Bailey, C. M., Zahran, H. S., King, M. E., Johnson, C. A., & Liu, X. (2012). National Surveillance of Asthma: United States, 2001–2010. National Center for Health Statistics. Vital and Health Statistics, 3(35), 1–67.
Naqvi, M., Thyne, S., Choudhry, S., Tsai, H. J., Navarro, D., Castro, R. A., … Burchard, E. G. (2007). Ethnic-specific differences in bronchodilator responsiveness among African Americans, Puerto Ricans, and Mexicans with asthma. Journal of Asthma, 44(8), 639–648. doi:10.1080/02770900701554441
Forno, E., Wang, T., Qi, C., Yan, Q., Xu, C. J., Boutaoui, N., … Celedón, J. C. (2019). DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study. The Lancet Respiratory Medicine, 7(4), 336–346. doi:10.1016/S2213-2600(18)30466-1
Rosenberg, S. L., Miller, G. E., Brehm, J. M., & Celedón, J. C. (2014). Stress and asthma: novel insights on genetic, epigenetic, and immunologic mechanisms. The Journal of allergy and clinical immunology, 134(5), 1009–1015. doi:10.1016/j.jaci.2014.07.005