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Nina Holland,¹ Clement Furlong,² Maria Bastaki,¹ Rebecca Richter,² Asa Bradman,¹ Karen Huen,¹ Kenneth Beckman,³ and Brenda Eskenazi¹

¹Center for Children's Environmental Health, School of Public Health, University of California, Berkeley, California, USA; ²Departments of Genome Sciences and Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA; ³Children's Hospital Research Institute, Oakland, California, USA

Abstract
Recent studies have demonstrated widespread pesticide exposures in pregnant women and in children. Plasma paraoxonase 1 (PON1) plays an important role in detoxification of various organophosphates. The goals of this study were to examine in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort of Latina mothers and their newborns living in the Salinas Valley, California, the frequencies of five PON1 polymorphisms in the coding region (192_QR and 55_LM) and the promoter region (–162_AG, –909_CG , and –108_CT) and to determine their associations with PON1 plasma levels [phenylacetate arylesterase (AREase) ] and enzyme activities of paraoxonase (POase) and chlorpyrifos oxonase (CPOase) . Additionally, we report results of PON1 linkage analysis and estimate the predictive value of haplotypes for PON1 plasma levels. We found that PON1_–909, PON1_–108, and PON1₁₉₂ had an equal frequency (0.5) of both alleles, whereas PON1_–162 and PON1₅₅ had lower variant allele frequencies (0.2) . Nearly complete linkage disequilibrium was observed among coding and promoter polymorphisms (p < 0.001) , except PON1₁₉₂ and PON1_–162 (p > 0.4) . Children's PON1 plasma levels (AREase ranged from 4.3 to 110.7 U/mL) were 4-fold lower than their mothers' (19.8 to 281.4 U/mL) . POase and CPOase activities were approximately 3-fold lower in newborns than in mothers. The genetic contribution to PON1 enzyme variability was higher in newborns (R² = 25.1% by genotype and 26.3% by haplotype) than in mothers (R² = 8.1 and 8.8%, respectively) . However, haplotypes and genotypes were comparable in predicting PON1 plasma levels in mothers and newborns. Most of the newborn children and some pregnant women in this Latino cohort may have elevated susceptibility to organophosphate toxicity because of their PON1₁₉₂ genotype and low PON1 plasma levels. Key words: chlorpyrifos, cord blood, haplotypes, Latino cohort, linkage disequilibrium, organophosphate, paraoxonase 1 (PON1) genotype, paraoxonase activity, pesticides, PON1 polymorphisms, pregnancy. Environ Health Perspect 114:985–991 (2006) . doi:10.1289/ehp.8540 available via http://dx.doi.org/ [Online 2 February 2006]

Address correspondence to N. Holland, 759 University Hall, School of Public Health, University of California, Berkeley, CA 94720-7360 USA. Telephone: (510) 455-0561. Fax: (510) 643-5426. E-mail: ninah@berkeley.edu

We gratefully acknowledge Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) staff, students, community partners, and especially the CHAMACOS participants and their families, without whom this study would not be possible. L. Barcellos's assistance with haplotype analysis and K. Kogut's and E. Weltzien's help with statistical analysis are sincerely appreciated.

This research was supported by National Institute of Environmental Health Sciences (NIEHS) grants P30 ESO1896, 2 P01 ES09605-06, 2 PO1 ES09601, and R01ES09883, National Institutes of Health (NIH) grant P60 MD00222, and by grants R82670901-5, RD-83170901, and R826886 from the U.S. Environmental Protection Agency (EPA) .

This article's contents are solely the responsibility of the authors and do not necessarily represent official views of the NIEHS, NIH, or the U.S. EPA.

The authors declare they have no competing financial interests.

Received 26 July 2005 ; accepted 2 February 2006.