Background Acetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a minor allele variant in the glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal acetaminophen exposure would predict wheeze at age 5 years in an inner-city minority cohort and examined whether this association was modified by common polymorphisms in genes related to the glutathione pathway.
Methods An ongoing population-based birth cohort study of Dominican Republic and African-American children in New York prospectively assessed the use of analgesics during pregnancy and current wheeze at age 5 years in 301 children. Genotyping was conducted for GST polymorphisms. Binomial regression was used to adjust for potential confounders including postnatal acetaminophen use.
Results 34% of mothers reported acetaminophen use during pregnancy and 27% of children had current wheeze at 5 years. Prenatal exposure to acetaminophen predicted current wheeze (multivariate relative risk 1.71; 95% CI 1.20 to 2.42; p=0.003), and the risk increased monotonically with increasing number of days of prenatal acetaminophen exposure (p trend <0.001). 68% of children had at least one copy of the GSTP1 minor allele (Val). The risk of wheeze was modified by GSTP1 (additive interaction p=0.009) and was observed only among children with the GSTP1 minor allele.
Conclusions Prenatal exposure to acetaminophen predicted wheeze at age 5 years in an inner-city minority cohort. The risk was modified by a functional polymorphism in GSTP1, suggesting a mechanism involving the glutathione pathway.
- glutathione S transferase
- asthma epidemiology
- paediatric asthma
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Funding This study was supported by the National Institute of Environmental Health Sciences (NIEHS) (grant #s P01 ES09600, 5 RO1 ES08977, RO1ES11158, P30 ES009089, P50ES015905), the U.S. Environmental Protection Agency (EPA) (grant #s R827027, RD-832141), Bauman Family Foundation, Gladys and Roland Harriman Foundation, New York Community Trust, Educational Foundation of America, The New York Times Company Foundation, The Schmidt Family Foundation, The Johnson Family Foundation, Rockefeller Financial Services, Horace W Goldsmith Foundation, Beldon Fund, The John Merck Fund and V Kann Rasmussen Foundation. GLC received funding as a NIH National Center on Minority Health and Health Disparities fellow. RGB was supported by a Robert Wood Johnson Generalist Faculty Scholars Award. Other funders: NIH.
Competing interests None.
Ethics approval The study was approved by Columbia University's Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
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