Public release date: 27-Mar-2013 [ | E-mail | Share ]
Contact: John Easton john.easton@uchospitals.edu 773-795-5225 University of Chicago Medical Center
About 90 percent of children with two copies of a common genetic variation and who wheezed when they caught a cold early in life went on to develop asthma by age 6, according to a study to be published March 28 by the New England Journal of Medicine.
These children, all from families with a history of asthma or allergies, were nearly four times as likely to develop the disease as those who lacked the genetic variation and did not wheeze. The effects of eachthe genetic variation and wheezing illness caused by a human rhinovirus infectionare not merely additive but also interactive, the authors say.
The genetic marker studied, a variation on chromosome 17, is common. Half of the children in the study had one copy and 25 percent had two. Colds caused by human rhinoviruses also are extremely common, affecting almost all infants. But the combination of genetic risk plus the wheezing response to rhinovirus infection by children under age 3 was tightly linked to the development of asthma by age 6.
"We found that the interaction between this specific wheezing illness and a gene or genes on a region of chromosome 17 determines childhood asthma risk," said study author Carole Ober, PhD, Blum-Riese Professor of Human Genetics at the University of Chicago. "The combination of genetic predisposition and the child's response to this infection has a huge effect."
Wheezing caused by respiratory syncytial virus (RSV), a more serious but less common childhood infection, did not show this same interaction.
Several genome-wide association studies have linked asthma to genetic variation on a region of chromosome 17, referred to as 17q21. Although this variation applies primarily to early-onset asthma, it still "dwarfs every other asthma-related genetic risk factor," Ober said.
Exactly how the genes and viral infection interact to cause asthma is unclear. Two genes in the 17q21 region may play a role. One of them, known as ORMDL3, is the "most likely candidate," Ober said. The protein produced by ORMDL3 is found in the endoplasmic reticulum membrane, the same component of airway cells that rhinovirus uses to makes more copies of itself. Less is known about the function of the second gene, GSDMB.
The researchers studied two carefully monitored cohorts of children from families at high risk for asthma. All of the 200 children in the COAST cohort, based at the University of Wisconsin under the leadership of Robert Lemanske, MD, principal investigator of the project, had at least one parent with asthma, respiratory allergies, or both. They were followed from birth and evaluated for asthma at age 6. The 297 Danish children in the COPSAC cohort were born to mothers with asthma and evaluated for asthma at age 7.
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Childhood asthma tied to combination of genes and wheezing illness