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Recent progress in the genetics and epigenetics of paraoxonase: why it is relevant to children's environmental health

Holland, Nina; Lizarraga, Daneida; Huen, Karen

Current Opinion in Pediatrics: April 2015 - Volume 27 - Issue 2 - p 240–247
doi: 10.1097/MOP.0000000000000192
THERAPEUTICS AND TOXICOLOGY: Edited by Robert O. Wright
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Purpose of review Children are more susceptible to exposures in utero and during early childhood that may result in developmental problems and chronic diseases. Novel discoveries in the field of molecular epidemiology that can help explain susceptibility to exposures and disease will be demonstrated using the multifunctional enzyme paraoxonase 1 (PON1) as an example.

Recent findings The broad PON1 variability in humans, partly due to differences in genetics and age, can confer differential susceptibility because this enzyme can detoxify organophosphate pesticides and has antioxidant properties. Epigenetics plays a significant role in the mediation of the effects of environmental exposure on human health and is hypothesized to be a major contributing factor to the early-life origins of adult disease. Studies highlighted in this review demonstrate the relationship of PON1 polymorphisms with microRNA binding in addition to a link between DNA methylation in the transcriptional regulatory region with changes in PON1 enzyme levels. Other important methodologies such as ancestry informative markers and lactonase activity can enhance studies involving PON1.

Summary This PON1 model demonstrates that integrating genetic and epigenetic factors, as well as other novel methodologies, can improve our understanding of important susceptibility factors linked to pediatric disease.

Environmental Health Sciences Division and the Center for Environmental Research and Children's Health, School of Public Health, University of California, Berkeley, California, USA

Correspondence to Dr Nina Holland, 50 University Hall, Berkeley, CA 94720–7360, USA. Tel: +1 510 455 0561; fax: +1 510 665 2202; e-mail: ninah@berkeley.edu

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