Genetic Variants and Wheezing Put Kids At Risk For Asthma

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Almost every toddler will sniffle through a cold by the time they are three, but if they wheeze while they’re sick, they may be at higher risk of developing asthma.

Previous research found that wheezing-related illnesses can increase a child’s risk for developing asthma, and other studies connected certain genetic factors to this heightened tendency to wheeze. In a new study published in the New England Journal of Medicine, researchers connected the two and found that 90% of three-year-olds with a combination of specific genes and a particular wheezing illness were diagnosed with asthma by the age of 6.

The scientists focused on a region of chromosome 17, known as 17q21 that has been associated with an elevated risk of asthma early in life. Two genes in the region likely increase this risk — ORMDL3 and GSDMB. Variants of these genes, which are relatively common, seemed to confer higher risk of wheezing when children were infected with the rhinovirus, which is responsible for the common cold. About half of the infants in the study had one copy of the variant, while a quarter had both copies, which significantly increased their likelihood of wheezing and developing asthma.

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The researchers included children from two separate study groups, all of whom came from families with a history of allergies or asthma. The first group included 200 children toddlers with at least one, and possibly two parents who had allergies or asthma while the second group consisted of Danish toddlers whose mothers were diagnosed with asthma. Among children without the high-risk genetic variants for asthma, 40% who wheezed when they caught a cold before age three developed asthma by age six, compared to 60% who had one copy of the variant and wheezed, and 90% of those who had two copies and also wheezed.

“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. The combination of genetic predisposition and the child’s response to this infection has a huge effect,” said study author Carole Ober, a Blum-Riese Professor of Human Genetics at the University of Chicago in a statement.

Overall, the children with the genetic and wheezing illness combination were almost four times as likely to develop asthma compared to kids who did not have the genetic variation or did not wheeze, suggesting that wheezing might be a relatively easy marker for identifying toddlers who might be at highest risk of developing asthma later.

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The biological mechanisms underlying the connection are not well understood, but to get a better idea of what’s going on, the researchers collected blood from 100 healthy adults and exposed their immune cells to human rhinovirus. Infection with the cold virus seemed to make the asthma-related genes on chromosome 17 more active, possibly leading to more wheezing.

If the results are confirmed, then doctors and parents could be more alert to early signs of wheezing, and consider testing for the presence of the genetic variants that could increase the risk of asthma. Such early intervention could help to limit exposure to asthma triggers, such as cigarette smoke, bisphenol A and other potential irritants, and hopefully reduce the severest symptoms as well.