Gene variants linked to childhood acetaminophen–asthma risk
medwireNews: Researchers have found several gene polymorphisms that are associated with an increased risk for childhood asthma after acetaminophen consumption in early life.
The study findings also showed that a family history of asthma mediated the risk, report authors Soo-Jong Hong (University of Ulsan Colleage of Medicine, Seoul, Korea) and colleagues.
The study, published in the Annals of Allergy, Asthma and Immunology, included 919 preschool children with a mean age of 4.9 years, of whom 46 (5.0%) had a parental history of asthma.
Among the 550 (60.7%) children who consumed acetaminophen for more than 3 days within the first year of life (acetaminophen use), the odds for asthma treatment within the previous year were 3.5-fold higher than in children who did not (6.0 vs 1.6%). However, there was no significant difference between the two groups with regard to ever having an asthma diagnosis, or current asthma.
The effects of acetaminophen use on asthma risk were even stronger in children with a parental history of asthma who had a 19.1-fold greater odds for asthma treatment in the previous 12 months than children with neither acetaminophen use or family history (25.0 vs 1.3%). These children also had a 4.1-fold, increased risk for asthma diagnosis ever (25.0 vs 5.0%), and a 5.1-fold increased risk for current asthma (14.3 vs 2.3%), respectively.
The researchers found that polymorphisms in three oxidative stress-related genes that have previously been associated with asthma were associated with a significantly increased risk for asthma following acetaminophen use. Children with polymorphisms in NAT2, Nrf2, and GSTP1 had a 5.1-, 3.7-, and 4.2-fold increased odds, respectively, for asthma treatment in the previous 12 months compared with children with the polymorphism but no paracetamol use.
The authors say that their finding of an association between acetaminophen use and asthma may be due to acetaminophen use during lower respiratory viral infections, which are associated with an increased risk for childhood asthma. The association may also be non-causal, as children with severe asthma typically require courses of acetaminophen for respiratory infections that may be related to their asthma.
However, in addition to its own potential antigenic effect, acetaminophen results in reduced glutathione levels, and may also promote the Th2 immune response through reduced cyclo-oxygenase inhibition, which could explain its association with asthma, explain Hong and colleagues.
Additionally, they found that children with a history of acetaminophen use and a family history of asthma had significantly higher mean eosinophil counts than children with neither history (5.3 vs 4.0%). The authors say this new finding may indicate a role for eosinophils in mediating the association between acetaminophen use and asthma.
"Further prospective, long-term follow-up studies are needed to confirm and extend these findings," the authors conclude.
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By Kirsty Oswald, medwireNews Reporter