Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma - 07/08/11
, Roger B. Newson, DPhil a, Susan M. Ring, PhD b, Matthew J. Rose-Zerilli, BSc d, John W. Holloway, PhD d, A. John Henderson, MD c
Reprint requests: Seif O. Shaheen, PhD, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Centre for Health Sciences, Barts and The London School of Medicine and Dentistry, 2 Newark Street, Whitechapel, London, E1 2AT, United Kingdom.Abstract |
Background |
Prenatal and infant acetaminophen exposure has been associated with an increased risk of childhood asthma phenotypes. Demonstration of biologically plausible interactions between these exposures and maternal and child antioxidant gene polymorphisms would strengthen causal inference.
Objective |
To explore potential interactions between prenatal and infant acetaminophen exposure and antioxidant genotypes on childhood asthma.
Methods |
In the Avon Longitudinal Study of Parents and Children, we typed a functional nuclear erythroid 2 p45-related factor 2 (Nrf2) polymorphism and glutathione S-transferase (GST) M1, T1, and P1 polymorphisms. Effects of prenatal and infant acetaminophen exposure on asthma phenotypes at 7 years were stratified by genotype in >4000 mothers and >5000 children.
Results |
Risk of asthma and wheezing associated with early gestation acetaminophen exposure was increased when maternal copies of the minor T allele of Nrf2 were present (P interactions, .02 and .04, respectively). Risk of asthma associated with late gestation exposure was higher when maternal GSTT1 genotype was present rather than absent (P interaction, .006), and risk of wheezing was increased when maternal GSTM1 was present (P interaction, .04). Although acetaminophen use in infancy was associated with an increased risk of atopy, child antioxidant genotype did not modify associations between infant acetaminophen use and asthma phenotypes. However, the increased risk of asthma and wheezing associated with late gestation acetaminophen exposure in the presence of maternal GSTM1 was further enhanced when GSTM1 was also present in the child.
Conclusion |
Maternal antioxidant gene polymorphisms may modify the relation between prenatal acetaminophen exposure and childhood asthma, strengthening evidence for a causal association. In contrast, relations between infant acetaminophen use and asthma and atopy were not modified by child genotype and may be confounded by pre-existing wheeze or allergy.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, acetaminophen, paracetamol, glutathione-S-transferase, Nrf2, prenatal exposure, delayed effects, ALSPAC, pregnancy, birth cohort, genotype, gene-environment interaction
Abbreviations used : ALSPAC, BMI, BR, FEF25-75, FVC, GST, NAPQI, Nrf2, OR, SNP
Plan
| The UK Medical Research Council, the Wellcome Trust, and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children. This study was funded by the British Lung Foundation. S.O.S. was an Asthma UK Senior Research Fellow. |
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| Disclosure of potential conflict of interest: S. O. Shaheen receives research support from Asthma UK and the Medical Research Council. R. B. Newson receives compensation from the UK Department of Health Policy Research Programme. S. M. Ring receives research support from the Wellcome Trust, the Medical Research Council, and the European Union. J. W. Holloway receives research support from the Medical Research Council UK and Asthma UK. A. J. Henderson receives research support from the Medical Research Council UK and the Wellcome Trust. M. J. Rose-Zerilli has declared that he has no conflict of interest. |
Vol 126 - N° 6
P. 1141 - décembre 2010 Retour au numéro
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