Pitt/Children’s Study: Exposure to Violence, Gene Changes Linked to Asthma In Puerto Rican Children

PITTSBURGH, PA - March 18, 2013 - 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 new study led by researchers at Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine. 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 both living in the island and in the U.S., said senior investigator Juan C. Celedón, M.D., Dr. P.H., chief, Division of Pediatric Pulmonology, Allergy and Immunology, Children's Hospital, and Niels K. Jerne Professor, Department of Pediatrics, Pitt School of Medicine. He 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," Dr. Celedón said. "We wanted to see whether similar gene alterations could be found among Puerto Rican children with asthma."

His team recruited children ages 6 to 14 years who had four Puerto Rican grandparents from randomly selected San Juan households; 271 had physician-diagnosed asthma and wheeze in the prior year and 266 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.

They looked for evidence of a biochemical process called methylation of the promoter, or "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," Dr. 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."

Co-authors of the paper include other researchers from Children's Hospital and the University of Pittsburgh, the University of Puerto Rico, and Harvard School of Public Health. The study was funded by National Institutes of Health grant R01HL079966 and Children's Hospital.

About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, seewww.medschool.pitt.edu.

About Children's Hospital of Pittsburgh of UPMC
Renowned for its outstanding clinical services, research programs and medical education, Children's Hospital of Pittsburgh of UPMC has helped establish the standards of excellence in pediatric care. From ambulatory care to transplantation and cardiac care, talented and committed pediatric experts care for infants, children and adolescents who make more than 1 million visits to Children's and its many neighborhood locations each year. Children's also has been named consistently to several elite lists of pediatric health care facilities, including ranking 7th among children's hospitals and schools of medicine (FY 2011) in funding provided by the National Institutes of Health, and is one of 12 pediatric hospitals in the United States named to U.S. News & World Report's Honor Roll of America's "Best Children's Hospitals" for 2012–2013.

Anita Srikameswaran, 412-578-9193, SrikamAV@upmc.edu

Andrea Kunicky, 412-692-6254, andrea.kunicky@chp.edu