Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease.
Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease.
复制标题
DOI：
10.1097/ede.0b013e3181c15ec6
复制
发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Ritz B
中科院分区：
文献类型：
--
作者：
Manthripragada AD;Costello S;Cockburn MG;Bronstein JM;Ritz B
人类、动物和细胞模型支持农药在帕金森病病因学中的作用。对农药的敏感性可能被外生酶的遗传变异所改变，如对氧磷酶，它在代谢某些有机磷中起作用。我们研究了帕金森病与有机磷二嗪农、毒死蜱和对硫磷之间的关系，以及PON1基因编码区55位功能多态性的影响（PON1-55）。从2001年1月1日至2008年1月1日，我们在一项基于人群的病例对照研究中，从加州三个农村县招募了351例病例和363例对照。参与者提供了DNA样本，并根据农药使用报告和地理信息系统（GIS）方法确定了居民对有机磷的暴露。我们在无条件logistic回归分析中评估了基因和农药的主要影响，并评估了携带PON1-55 MM变异对二嗪农、毒死蜱和对硫磷暴露的影响。变异MM PON1-55基因型携带者暴露于有机磷后，帕金森病风险比野生型或杂合子基因型未暴露者增加2倍以上（二嗪农的比值比为2.2[95%可信区间= 1.1-4.5]；毒死蜱的比值比为2.6[1.3-5.4]）。毒死蜱对年轻发病病例和对照组（≤60岁）的影响更为明显（5.3[1.7-16]）。对硫磷没有增加患病风险。我们在PON1-55变异携带者中观察到PON1代谢的特定有机磷的风险增加，这强调了在研究帕金森病的环境暴露时考虑易感因素的重要性。
Human, animal and cell models support a role for pesticides in the etiology of Parkinson disease. Susceptibility to pesticides may be modified by genetic variants of xenobiotic enzymes, such as paraoxonase, that play a role in metabolizing some organophosphates. We examined associations between Parkinson disease and the organophosphates diazinon, chlorpyrifos, and parathion, and the influence of a functional polymorphism at position 55 in the coding region of the PON1 gene (PON1-55). From 1 January 2001 through 1 January 2008, we recruited 351 incident cases and 363 controls from three rural California counties in a population-based case-control study. Participants provided a DNA sample, and residential exposure to organophosphates was determined from pesticide usage reports and a geographic information system (GIS) approach. We assessed the main effects of both genes and pesticides in unconditional logistic regression analyses, and evaluated the effect of carrying a PON1-55 MM variant on estimates of effects for diazinon, chlorpyrifos, and parathion exposures. Carriers of the variant MM PON1-55 genotype exposed to organophosphates exhibited a greater than 2-fold increase in Parkinson disease risk compared with persons who had the wildtype or heterozygous genotype and no exposure (for diazinon, odds ratio = 2.2 [95% confidence interval = 1.1–4.5]; for chlorpyrifos, 2.6 [1.3–5.4]). The effect estimate for chlorpyrifos, was more pronounced in younger-onset cases and controls (≤60 years) (5.3 [1.7–16]). No increase in risk was noted for parathion. The increase in risk we observed among PON1-55 variant carriers for specific organophosphates metabolized by PON1 underscores the importance of considering susceptibility factors when studying environmental exposures in Parkinson disease.