title: Recent progress in the genetics and epigenetics of paraoxonase: why it is relevant to children's environmental health.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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: Environmental Health Sciences Division and the Center for Environmental Research and Children's Health, School of Public Health, University of California, Berkeley, California, USA.
authors: Nina
authors: N
authors: Holland
authors: Daneida
authors: D
authors: Lizarraga
authors: Karen
authors: K
authors: Huen
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics*; D002648:Child; D004198:Disease Susceptibility; D004781:Environmental Exposure / Q000517:prevention & control*; D004782:Environmental Health; D057890:Epigenomics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D011247:Pregnancy; D015995:Prevalence
chemical_list: D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
references: J Allergy Clin Immunol. 2014 Feb;133(2):370-8
references: 23992748
references: Nat Biotechnol. 2009 Apr;27(4):361-8
references: 19329998
references: Pharmacogenetics. 2000 Jul;10(5):453-60
references: 10898114
references: Pharmacogenomics. 2003 Jul;4(4):431-41
references: 12831322
references: Environ Health Perspect. 2009 Oct;117(10):1632-8
references: 20019917
references: Nat Rev Genet. 2005 Aug;6(8):597-610
references: 16136652
references: Genomics. 1996 May 1;33(3):498-507
references: 8661009
references: Environ Health Perspect. 2010 Dec;118(12):1775-81
references: 21126941
references: Epigenetics. 2012 Oct;7(10):1094-7
references: 22948233
references: Science. 2001 Jul 20;293(5529):489-93
references: 11452081
references: PLoS One. 2011;6(8):e23923
references: 21904599
references: Toxicol Appl Pharmacol. 2010 Apr 15;244(2):181-9
references: 20045427
references: Clin Biochem. 2013 Dec;46(18):1830-6
references: 24028901
references: Am J Hum Genet. 2001 Jun;68(6):1428-36
references: 11335891
references: Med Res Rev. 2012 Mar;32(2):326-48
references: 22383180
references: J Lipid Res. 2005 Jun;46(6):1239-47
references: 15772423
references: J Lipid Res. 2008 Jan;49(1):245-50
references: 17906223
references: Adv Clin Exp Med. 2013 Mar-Apr;22(2):229-36
references: 23709379
references: Environ Health Perspect. 2006 Jul;114(7):985-91
references: 16835048
references: Environ Res. 2014 Oct;134:149-57
references: 25171140
references: Int J Mol Sci. 2012;13(7):8259-72
references: 22942701
references: J Mol Med (Berl). 2003 Dec;81(12):766-79
references: 14551701
references: Reprod Toxicol. 2007 Apr-May;23(3):267-82
references: 17317097
references: Nucleic Acids Res. 2014 Jan;42(Database issue):D68-73
references: 24275495
references: Crit Rev Clin Lab Sci. 2009;46(2):83-106
references: 19255916
references: J Lipid Res. 2013 Feb;54(2):552-60
references: 23160181
references: PLoS One. 2010;5(2):e9040
references: 20140262
references: J Lipid Res. 2000 Aug;41(8):1358-63
references: 10946025
references: Genes Dev. 2002 Jan 1;16(1):6-21
references: 11782440
references: Environ Health Perspect. 2003 Aug;111(11):1403-9
references: 12928148
references: PLoS One. 2013;8(5):e62565
references: 23658746
references: J Genet. 2010 Dec;89(4):417-23
references: 21273692
references: Atherosclerosis. 2013 May;228(1):161-7
references: 23497787
references: Pediatr Res. 2010 Mar;67(3):309-13
references: 19915520
references: Biochem J. 2003 Jun 1;372(Pt 2):643-9
references: 12639220
references: EXCLI J. 2014 Apr 09;13:416-26
references: 26417268
references: Genome Res. 2006 Sep;16(9):1075-83
references: 16899657
references: Biomarkers. 2003 Jan-Feb;8(1):1-12
references: 12519632
references: Nat Genet. 1993 Jan;3(1):73-6
references: 8098250
references: Br J Nutr. 2013 Nov 14;110(9):1639-47
references: 23789921
references: J Mol Biol. 1987 Jul 20;196(2):261-82
references: 3656447
references: J Am Med Inform Assoc. 2012 Mar-Apr;19(2):156-60
references: 22101905
references: Environ Mol Mutagen. 2011 Mar;52(2):105-16
references: 20839225
references: Neurodegener Dis. 2008;5(3-4):225-7
references: 18322397
references: Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2441-7
references: 11073850
references: Am J Physiol Heart Circ Physiol. 2012 Nov 1;303(9):H1085-95
references: 22942181
references: PLoS One. 2012;7(5):e36830
references: 22615820
references: Obesity (Silver Spring). 2010 Jun;18(6):1079-84
references: 19834469
references: Nature. 2009 Nov 19;462(7271):315-22
references: 19829295
references: Am J Epidemiol. 2009 Feb 15;169(4):389-400
references: 19139055
references: Mol Aspects Med. 2013 Jul-Aug;34(4):753-64
references: 22906839
references: Toxicol Appl Pharmacol. 2005 Jun 15;205(3):282-9
references: 15922013
references: Curr Med Chem. 2011;18(36):5624-43
references: 22172068
references: Mol Oncol. 2012 Dec;6(6):567-78
references: 22902148
references: J Expo Sci Environ Epidemiol. 2012 Nov;22(6):641-8
references: 22760442
references: Cell. 2009 Jan 23;136(2):215-33
references: 19167326
references: J Physiol Biochem. 2014 Jun;70(2):603-14
references: 24500802
references: Redox Rep. 2014 May;19(3):124-32
references: 24620935
references: Horm Res. 2009 Jan;71 Suppl 1:13-6
references: 19153498
references: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006 Nov;150(2):205-15
references: 17426780
references: Science. 2001 Aug 10;293(5532):1064-7
references: 11498570
references: JAMA. 2008 Mar 19;299(11):1265-76
references: 18349088
references: Nat Genet. 2009 Feb;41(2):178-86
references: 19151715
references: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13556-61
references: 18768788