Nina Holland1, Daneida Lizarraga, Karen Huen. 1. Environmental Health Sciences Division and the Center for Environmental Research and Children's Health, School of Public Health, University of California, Berkeley, California, USA.
Abstract
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.
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.
Authors: J C Stephens; J A Schneider; D A Tanguay; J Choi; T Acharya; S E Stanley; R Jiang; C J Messer; A Chew; J H Han; J Duan; J L Carr; M S Lee; B Koshy; A M Kumar; G Zhang; W R Newell; A Windemuth; C Xu; T S Kalbfleisch; S L Shaner; K Arnold; V Schulz; C M Drysdale; K Nandabalan; R S Judson; G Ruano; G F Vovis Journal: Science Date: 2001-07-12 Impact factor: 47.728
Authors: Katherine A Drake; Dara G Torgerson; Christopher R Gignoux; Joshua M Galanter; Lindsey A Roth; Scott Huntsman; Celeste Eng; Sam S Oh; Sook Wah Yee; Lawrence Lin; Carlos D Bustamante; Andrés Moreno-Estrada; Karla Sandoval; Adam Davis; Luisa N Borrell; Harold J Farber; Rajesh Kumar; Pedro C Avila; Emerita Brigino-Buenaventura; Rocio Chapela; Jean G Ford; Michael A Lenoir; Fred Lurmann; Kelley Meade; Denise Serebrisky; Shannon Thyne; William Rodríguez-Cintrón; Saunak Sen; José R Rodríguez-Santana; Ryan D Hernandez; Kathleen M Giacomini; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2013-08-29 Impact factor: 10.793
Authors: Brenda Eskenazi; Karen Huen; Amy Marks; Kim G Harley; Asa Bradman; Dana Boyd Barr; Nina Holland Journal: Environ Health Perspect Date: 2010-12 Impact factor: 9.031
Authors: Karen Huen; Kim Harley; Jordan Brooks; Alan Hubbard; Asa Bradman; Brenda Eskenazi; Nina Holland Journal: Environ Health Perspect Date: 2009-06-09 Impact factor: 9.031
Authors: Madeleine P Ball; Jin Billy Li; Yuan Gao; Je-Hyuk Lee; Emily M LeProust; In-Hyun Park; Bin Xie; George Q Daley; George M Church Journal: Nat Biotechnol Date: 2009-03-29 Impact factor: 54.908
Authors: Irma Martha Medina-Díaz; Néstor Ponce-Ruíz; Aurora Elizabeth Rojas-García; José Francisco Zambrano-Zargoza; Yael Y Bernal-Hernández; Cyndia Azucena González-Arias; Briscia S Barrón-Vivanco; José Francisco Herrera-Moreno Journal: Antioxidants (Basel) Date: 2022-03-31
Authors: Sara Diels; Bart Cuypers; Asta Tvarijonaviciute; Bruno Derudas; Evelien Van Dijck; An Verrijken; Luc F Van Gaal; Kris Laukens; Philippe Lefebvre; Jose J Ceron; Sven Francque; Wim Vanden Berghe; Wim Van Hul Journal: Clin Epigenetics Date: 2021-08-13 Impact factor: 6.551