Background: Acetaminophen has been associated with asthma and is in part metabolized 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 hypothesized 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 and African-American children in New York prospectively assessed 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: Thirty-four percent of mothers reported acetaminophen use during pregnancy and 27% of children had current wheeze at 5 years. Prenatal acetaminophen exposure predicted current wheeze (multivariate relative risk, 1.71; 95% CI 1.20-2.42; P=0.003) and the risk increased monotonically with increasing number of days of prenatal acetaminophen exposure (P-trend <0.001). Sixty-eight percent 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 acetaminophen exposure 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.