Center for Environmental Research and Children's Health, School of Public Health, University of California, Berkeley, California, United States of America.
PLoS One. 2011;6(8):e23923. doi: 10.1371/journal.pone.0023923. Epub 2011 Aug 31.
Epidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association.
The study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1(192) and PON1(-108)) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records.
Infants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON1(-108TT) genotype had shorter gestational age (β = -0.5 weeks, 95% Confidence Interval (CI): -0.9, 0.0) and smaller head circumference (β = -0.4 cm, 95% CI: -0.7, 0.0) than those with the PON1(-108CC) genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1(-108TT) genotype (p-value(interaction) = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-value(interaction) = 0.06) and head circumference (p-value(interaction)<0.01) in infants with non-susceptible genotypes.
Infants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth.
流行病学研究表明，母体有机磷（OP）农药暴露与胎儿生长较差有关，但研究结果不一致。我们探讨了在这种关联中，一种参与 OP 解毒的关键酶——对氧磷酶（PON1）是否可以作为一个效应修饰物。
该研究人群包括在加利福尼亚州一个农业区生活的母亲和儿童的 CHAMACOS 研究中的 470 名孕妇。我们分析了母亲在怀孕期间两次采集的尿液样本中 OP 农药的二烷基磷酸（DAP）代谢物。我们分析了母亲和胎儿（脐带）血样本中的 PON1 基因型（PON1(192)和 PON1(-108))和酶活性（对氧磷酶和芳基酯酶）。婴儿的出生体重、头围和胎龄从病历中获得。
婴儿的 PON1 基因型和活性与出生结局有关，但母亲的 PON1 基因型和活性与出生结局无关。易感 PON1(-108TT)基因型的婴儿胎龄较短（β= -0.5 周，95%置信区间（CI）：-0.9，0.0），头围较小（β= -0.4 厘米，95%置信区间（CI）：-0.7，0.0）比 PON1(-108CC)基因型的婴儿。婴儿的芳基酯酶和对氧磷酶活性与胎龄呈正相关。DAP 存在一定的效应修饰作用：只有易感 PON1(-108TT)基因型婴儿的母亲 DAP 浓度与胎龄较短相关（交互作用的 p 值= 0.09）。然而，非易感基因型婴儿的母亲 DAP 浓度与较大的出生体重（交互作用的 p 值= 0.06）和头围（交互作用的 p 值<0.01）相关。
PON1 基因型和酶活性水平表明婴儿可能更容易受到 OP 农药暴露影响的婴儿，其胎儿生长和胎龄较短。PON1 可能是导致早产或低出生体重的另一个因素。
