B89 - How do genes modify the prenatal effects of tobacco smoke paracetamol and antioxidant exposures on childhood respiratory outcomes - 01/12/2002

B number: 
Principal applicant name: 
Prof Seif Shaheen (King's College London, UK)
Prof Marcus Pembrey (UCL Institute of Child Health, London, UK), Prof John Henderson (University of Bristol, UK), Prof John Holloway (University of Southampton, UK)
Title of project: 
How do genes modify the prenatal effects of tobacco smoke, paracetamol and antioxidant exposures on childhood respiratory outcomes?
Proposal summary: 

The extent to which oxidant exposures such as tobacco smoke and paracetamol are detrimental, and antioxidants are

beneficial, to lung health, will depend partly on variation in genes involved in antioxidant defences and xenobiotic

metabolism and detoxification. However, few epidemiological studies have explored interactions between such genes

and oxidant/antioxidant exposures on childhood respiratory outcomes.

We will study how relevant gene polymorphisms in the mother and child modify effects of prenatal and postnatal

exposure to tobacco smoke, paracetamol and antioxidants on childhood lung function, wheezing, asthma and

bronchial hyper-responsiveness, in the Avon Longitudinal Study of Parents and Children, a large population-based

birth cohort, which has collected DNA from mothers as well as from children.

Confirmation of interactions between oxidant/antioxidant exposures and gene variants which influence antioxidant

function and xenobiotic toxicity would provide stronger evidence that the effects of the environmental risk factors are

causal, and may provide insights into mechanisms. By increasing our understanding of the early life influences on lung

development we hope to devise new strategies aimed at the primary prevention of lung disease in children and the

optimisation of their respiratory health.

Date proposal received: 
Sunday, 1 December, 2002
Date proposal approved: 
Sunday, 1 December, 2002
Allergies, Genetics, Respiratory, Atopy, Drugs, Smoking, Genes
Primary keyword: