Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns.
Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns.
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拉丁裔母亲和新生儿中的多态性，单倍型和酶活性。
DOI：
10.1289/ehp.8540
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发表时间：
2006-07
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
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作者：
最近的研究表明，孕妇和儿童普遍接触农药。血浆对氧磷酶1（PON 1）在多种有机磷农药的解毒过程中起重要作用。本研究的目的是在萨利纳斯母亲和儿童健康评估中心检查（CHAMACOS）出生队列的拉丁母亲和他们的新生儿生活在萨利纳斯谷，加州，编码区的五个PON 1多态性的频率（192 QR和55 LM）和启动子区（−162AG，−909CG，和-108CT），并确定其与PON 1血浆水平[苯乙酸芳基酯酶（AREase）]和对氧磷酶（POase）的酶活性的相关性和毒死蜱氧磷酶（CPOase）。此外，我们报告了PON 1连锁分析的结果，并估计单倍型对PON 1血浆水平的预测价值。我们发现PON 1 - 909、PON 1 - 108和PON 1192的两个等位基因的频率相等（0.5），而PON 1 - 162和PON 155的变异等位基因频率较低（0.2）。除了PON 1192和PON 1 −162（p > 0.4）外，在编码和启动子多态性之间观察到几乎完全的连锁不平衡（p < 0.001）。儿童的PON 1血浆水平（AREase范围为4.3至110.7 U/mL）比其母亲（19.8至281.4 U/mL）低4倍。POase和CPOase活性在新生儿中比在母亲中低约3倍。对PON 1酶变异的遗传贡献在新生儿中（R2 = 25.1%基因型和26.3%单倍型）高于母亲（R2 = 8.1和8.8%，分别）。然而，单倍型和基因型在预测母亲和新生儿血浆PON 1水平方面具有可比性。在这个拉丁裔队列中，大多数新生儿和一些孕妇可能对有机磷中毒的易感性升高，因为他们的PON 1192基因型和低PON 1血浆水平。
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 (192QR and 55LM) and the promoter region (−162AG, −909CG, and −108CT) 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.