Children who take paracetamol before the age of two years may face an increased risk of developing asthma by the age of 18, especially if they have specific variants in one particular gene, a European conference will hear today.
Delegates at the European Respiratory Society International Congress will hear from Ms Xin Dai that the link between paracetamol use and asthma seemed strongest in those who had a particular variant of the glutathione S-transferase (GST) gene, GSTP1.
However, the research showed only that there was an association between paracetamol and asthma, not that paracetamol caused the condition. She also found that another GST gene variant, GSTM1, was linked with reduced lung function.
GST genes contain the instructions for making enzymes that use glutathione to mop up the effects of exposure to toxins in the body and the lungs, preventing damage to cells and inflammation.
However, paracetamol consumes glutathione, thus reducing the body’s capacity to deal with toxic exposure.
“We hypothesised that people who did not have full GST enzyme activity because of common genetic variations or deletions may be more susceptible to adverse effects on the lungs from paracetamol use,” said Ms Dai, who is a nurse and PhD candidate at the Allergy and Lung Health Unit at the University of Melbourne, Australia.
She and her colleagues investigated their hypothesis in 620 children who had been followed from birth to 18 years old as part of the Melbourne Atopy Cohort Study.
A research nurse rang the family every four weeks for the first 15 months, followed up at 18 months and at two years old to ascertain how many days in the previous weeks the child had taken paracetamol.
When the children reached 18 years old, they gave a blood or saliva sample, which was tested for variants of the GST genes: GSTT1, GSTM1 and GSTP1. They were also assessed for asthma, and a spirometry test was performed to measure the amount of air inhaled and exhaled when breathing through a mouthpiece.
One variant of the GSTP1 gene, GSTP1 Ile/Ile, in which the amino acid Isoleucine is inherited from both parents, was associated with a higher risk of developing asthma.
Ms Dai said: “We found that children with the GSTP1 Ile/Ile variant had 1.8 times higher risk of developing asthma by the age of 18 years for each doubling of the days of paracetamol exposure when compared to children who were less exposed,” said Ms Dai. “In contrast, increasing paracetamol exposure in children who had other types of GSTP1 did not alter the risk of asthma.
“We also found effects in children who had a variant of GSTM1 in which one part is not functioning. In these children increasing paracetamol use was associated with small, but significant reduction in the amount of air they could forcibly breathe out in one second at 18 years.
“It is not known if the relationship we found between paracetamol use and lung function is clinically important. In addition, we found some weak evidence that paracetamol use in the first two years of life may be associated with reduced lung function in adolescence regardless of which variants of the GST genes the children had.”
She said their study adds to the growing body of evidence that the GST superfamily of genes, including three major classes –GSTM1, GSTT1 and GSTP1 – are associated with various diseases, such as cancers, asthma, atherosclerosis, allergies, Alzheimer’s and Parkinson’s disease.
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