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  • 标题:Paraoxonase Polymorphisms, Haplotypes, and Enzyme Activity in Latino Mothers and Newborns
  • 作者:Nina Holland ; Clement Furlong ; Maria Bastaki
  • 期刊名称:Environmental Health Perspectives
  • 印刷版ISSN:0091-6765
  • 电子版ISSN:1552-9924
  • 出版年度:2006
  • 卷号:114
  • 期号:7
  • 页码:985-991
  • DOI:10.1289/ehp.8540
  • 语种:English
  • 出版社:OCR Subscription Services Inc
  • 摘要: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 PON1 192 had an equal frequency (0.5) of both alleles, whereas PON1 162 and PON1 55 had lower variant allele frequencies (0.2). Nearly complete linkage disequilibrium was observed among coding and promoter polymorphisms ( p < 0.001), except PON1 192 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 ( R 2 = 25.1% by genotype and 26.3% by haplotype) than in mothers ( R 2 = 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 PON1 192 genotype and low PON1 plasma levels.
  • 关键词:chlorpyrifos; cord blood; haplotypes; Latino cohort; linkage disequilibrium; organophosphate; paraoxonase 1 (PON1) genotype; paraoxonase activity; pesticides; PON1 polymorphisms; pregnancy
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