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Study Identifies Children Genetically Susceptible To Environmental Triggers for Asthma

Monday, November 10, 2008

A new study has identified which children -- based on their genetic makeup -- might be most susceptible to environmental triggers for asthma, a finding that has implications for  asthma prevention and treatment.

The Cincinnati Children’s Hospital Medical Center study shows that children with a particular form of gene are more likely to have persistent wheezing if exposed to diesel exhaust, environmental tobacco smoke or mold by 24 months of age. The study, published online in the Journal of Pediatrics, is believed to be the first to investigate the interplay between genes and complex environmental factors on wheezing, over time, in early childhood.

"Delineating the factors that are contributory or protective to persistent wheezing in early childhood is critical to advance our understanding of asthma," says Gurjit Khurana Hershey, MD, PhD, director of asthma research at Cincinnati Children’s and senior author of the study. "Our study provides evidence that high levels of environmental exposures in children increased their risk of wheezing at 12 months and 24 months – but only in children with the GST-P1 Val105 polymorphism, whose link to asthma is well known."

Asthma is a complex heritable disease: There are a number of genes that contribute to a person's susceptibility, and chromosomes five, six, 11, 14 and 12 have all been implicated. GST-P1 Val105  is located on chromosome 11, a known "hot spot" for asthma-related genes.

"The lung undergoes critical development in infancy and early childhood, and asthma symptoms are just beginning to develop," says Dr. Hershey. "Early childhood wheezing and early persistent wheezing may be a precursor to asthma in these children. The GST-P1 genotype should be considered when evaluating asthma and wheezing in young children exposed to high levels of diesel exhaust particles, environmental tobacco smoke or visible mold in the home."

The study involved 570 infants enrolled in the Cincinnati Childhood Allergy and Air Pollution Study, a longitudinal study examining high-risk children with at least one parent prone to allergies. Families from a seven-county area in and near Cincinnati were recruited into the study based on the proximity of their homes to truck and bus traffic. Approximately four of five participants were non-Caucasian, and 87 percent of these were African-Americans.

Diesel particulates were measured at 24 sampling sites in the Cincinnati area, and a statistical model was used to derive an estimate of each child’s exposure. Environmental tobacco smoke exposure was determined by questionnaire, and each child’s home was evaluated by a trained professional for visible mold.

The researchers found that non-Caucasian infants were more likely to have higher exposure to diesel exhaust particles and have visible mold in their homes. Environmental tobacco smoke exposure was similar between the two groups. Wheezing at 24 months was significantly increased in the non-Caucasian group. After adjusting by genotype, however, race was not found to be a significant factor in evaluating the independent associations of each environmental exposure at 12 months of age.

On the other hand, both environmental tobacco smoke exposure and diesel exposure were associated with wheezing at both 12 and 24 months.  Mold exposure increased the risk of wheezing at 24 months, but not at 12 months.  

When researchers evaluated the relationship of "total environmental load" with wheezing, infants with multiple exposures were more likely to persistently wheeze, regardless of their genotype. "Clearly, long-term exposure to more pollutants places infants at greater risk, probably because a genotype that normally protects against wheezing (GST-P1 Ile105) is overwhelmed by the total exposure."

GST-P1 is a multifunctional enzyme in the surface (epithelial) tissues of the lung that has an important role in detoxification and inflammatory control.  Environmental exposures lead to a chemical change in the enzyme --as well as the gene that controls, or regulates it -- that blocks or inhibits detoxication and inflammation control.

The study was supported by grants from the National Institute of Environmental Health Sciences, an agency of the National Institutes of Health.

Cincinnati Children's Hospital Medical Center is one of America’s top three children’s hospitals for general pediatrics and is highly ranked for its expertise in digestive diseases, respiratory diseases, cancer, neonatal care, heart care and neurosurgery, according to the annual ranking of best children's hospitals by U.S. News & World Report. One of the three largest children’s hospitals in the U.S., Cincinnati Children’s is affiliated with the University of Cincinnati College of Medicine and is one of the top two recipients of pediatric research grants from the National Institutes of Health.

For its achievements in transforming healthcare, Cincinnati Children's is one of six U.S. hospitals since 2002 to be awarded the American Hospital Association-McKesson Quest for Quality Prize® for leadership and innovation in quality, safety and commitment to patient care. The hospital is a national and international referral center for complex cases, so that children with the most difficult-to-treat diseases and conditions receive the most advanced care leading to better outcomes.