Celedón-Led Pitt/Children’s Hospital Study Is First to Examine Links Between Asthma, Stress, and Gene Variation

Puerto Rican children who have asthma are more likely to be exposed to violence and to have changes in a gene that is associated with stress, according to a study led by researchers in the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC. The study, which is the first to examine the links between asthma, stress, and gene variation, was recently published in the American Journal of Respiratory and Critical Care Medicine.

Asthma rates are known to be higher among Puerto Rican children  living on the island and in the U.S., said senior investigator Juan C. , a professor of internal medicine and the Niels K. Jerne Professor of Pediatrics in the Pitt School of Medicine as well as chief of the Division of Pediatric Pulmonology, Allergy and Immunology in Children’s Hospital. Celedón and his colleagues have been studying these high-risk children to better understand their elevated asthma rates. In a previous project in Puerto Ricans, they found that psychosocial stress in a parent increased asthma symptoms in their children.

“Recently, there was a University of California study that showed traumatic life experiences affect a certain gene product involved in cellular stress responses in adults and was linked to a higher risk of post-traumatic stress disorder, or PTSD,” Celedón said. “We wanted to see whether similar gene alterations could be found among Puerto Rican children with asthma.”

Celedón’s team recruited children from randomly selected San Juan households who were between 6 and 14 years of age and had four Puerto Rican grandparents. In the group were 271 children who had physician-diagnosed asthma and wheezing in the prior year and 266 who did not have asthma or a history of wheezing. Blood samples were drawn for DNA analysis, all parents completed a questionnaire, and children 9 years and older answered another standard questionnaire about exposure to violence.

Researchers looked for evidence of a biochemical process called methylation of the promoter, or an “on-off” switch, of a gene called ADCYAP1R1, which the California study linked to PTSD. They found that increased methylation was associated with higher odds of having asthma and with exposure to violence, and that increasing exposure to violence was linked with a greater risk of asthma. They showed that a certain variation, or polymorphism, in the ADCYAP1R1 gene in study participants was also associated with asthma, but not with methylation.

“It appears there is a subgroup of people who may be more susceptible to asthma because of exposure to violence, and we need to understand how that happens,” Celedón said. “Most asthma studies have focused on environmental factors such as air pollution. This is one of the first to look at the impact of stress on epigenetics, which can cause differences in gene expression.”

Coauthors of the paper include other researchers from Children’s Hospital and the University of Pittsburgh, as well as researchers from the University of Puerto Rico and the Harvard School of Public Health.