Genetic analysis of organophosphate metabolism in NC farmworkers

NC农场工人有机磷代谢的遗传分析

• 批准号: 7489334
• 负责人: TIMOTHY D HOWARD
• 金额: $ 7.25万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7489334
• 关键词: 7q21; Accounting; Acute; Agriculture; Ancillary Study; Behavior; Blood; Cardiovascular system; Cessation of life; Chlorpyrifos; Cholinesterases; Chromosomes; Chronic; Class; Clothing; Coma; Communities; Condition; Congenital Abnormality; Cytochrome P450; DNA; Data; Diazinon; Dimethoate; Disease; Disulfoton; Dose; Enrollment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Enzymes; Exanthema; Exposure to; Factor Analysis; Family; Functional disorder; Funding; Gene Cluster; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomics; Genotype; Goals; Haplotypes; Health; Heart; Home environment; Housing; Human; Individual; Institutes; International; Lead; Link; Literature; Long-Term Effects; Lung; Malignant Neoplasms; Measures; Mediating; Metabolism; Nausea; Neurodegenerative Disorders; Neurologic; North Carolina; Occupational; Organophosphates; Pesticides; Phosmet; Population; Proteins; Rate; Recruitment Activity; Reporting; Risk; Saliva; Sampling; Seasons; Single Nucleotide Polymorphism; Source; Spouses; Sterility; Time; Toxic effect; Toxin; Unemployment; United States; Variant; Vision; Work; aryldialkylphosphatase; enzyme activity; farm worker; genetic analysis; genetic association; organophosphorus insecticide; pesticide exposure; programs; toxic organophosphate insecticide exposure; urinary

DESCRIPTION (provided by applicant): Farmworker exposure to pesticides is a widely acknowledged environmental health problem (Arcury et al., 2002; Arcury & Quandt 2003; Reeves & Schafer 2003; Arcury et al., 2006b). Organophosphorus (OP) insecticides are among the most widely used pesticides, and include chlorpyrifos, diazinon, dimethoate, disulfoton, and phosmet. Exposure to OP pesticides is detrimental to human health (Reigart & Roberts 1999), with immediate effects of limited exposure including rash, nausea, and blurry vision, and immediate effects of significant exposure including loss of continence, coma, and death. Delayed effects of exposure may include sterility, birth defects, cancer, and neurodegenerative disease. Sources of pesticide exposure among farmworkers and their families include occupational, para-occupational, residential, and environmental factors (Fenske et al., 2000; Arcury et al., 2006c; Quandt et al., 2006). Farmworkers have little to no control of their exposure (Austin et al., 2001), and have limited access to facilities at work for changing out of work clothes and showering before coming home (United States General Accounting Office (GAO) 2000; Arcury et al., 2001). The housing available to farmworkers is often located near fields to which pesticides are applied (Housing Assistance Council 2001; Early et al., 2006) and is generally substandard, with infestations that lead to residential pesticide application (Quandt et al., 2004; Early et al., 2006). Farmworkers and their spouses are often not provided with the information they need to protect themselves and their families from exposure (Arcury et al., 1999; Rao et al., 2006). The effective dose of pesticide exposure is clearly dependent on the initial environmental exposure, but it is also influenced by an individual's innate ability to metabolize and excrete the toxins. Metabolism of OP pesticides is primarily determined by specific proteins in the cytochrome P450 family and the paraoxonase class of molecules. Several of these genes are clustered in the same chromosomal region, indicating a potential common regulatory mechanism, which may be mediated by genetic variation within or between these genes. Polymorphisms in PON1 have been reported to be correlated with the levels of PON1 enzyme (e.g., (Holland et al., 2006)), suggesting that genetic variation contributes to the level or activity of this enzyme. A comprehensive analysis of the entire PON locus, containing PON1, PON2, and PON3, is necessary to identify the individual single nucleotide polymorphisms (SNPs) or combinations of SNPs that contribute to individual variability in OP metabolism. It has been suggested that lower levels of PON1 activity lead to an increased risk of the damaging effects of OP exposure. The goal of this study is to thoroughly characterize genetic variation of the specific p450 genes involved in OP metabolism and the entire PON locus in an effort to identify those individuals most at risk to the negative health effects of chronic organophosphate exposure. Pesticide exposure is an environmental health problem with both acute and chronic risks to farmworkers. The risk to any given individual can be expressed as an interaction between the quantity of the exposure itself and the rate at which that individual is able to metabolize and detoxify the pesticide. To fully understand the links between pesticide exposure and behavior or environmental factors, analyses must be able to consider genetic variability in pesticide metabolism. The goal of this study is to evaluate the genetic contribution of pesticide metabolism in a population of North Carolina farmworkers, in order to gain a more complete understanding of the potential for long term effects of chronic pesticide exposure.

描述（由申请人提供）：农民接触农药是一个广泛认可的环境健康问题（Arcury等，2002； Arcury＆Quandt 2003; Reeves＆Schafer 2003; Arcury et al。，2006b）。有机磷（OP）杀虫剂是使用最广泛的农药之一，包括毒死rif虫，二氧zin，二甲酸盐，二硫代蛋白，二硫代和phosmet。暴露于OP农药对人类健康有害（Reigart＆Roberts，1999年），直接影响有限的影响，包括皮疹，恶心和视力模糊，以及重大暴露的立即影响，包括持续性，昏迷和死亡的丧失。暴露的延迟作用可能包括无菌性，出生缺陷，癌症和神经退行性疾病。农场工人及其家庭中农药暴露的来源包括职业，职业，住宅和环境因素（Fenske等，2000； Arcury等，2006c； Quandt等，2006）。农场工人几乎无法控制自己的曝光率（Austin等，2001），并且在回家之前换衣服和淋浴的设施有限（美国一般会计办公室（GAO）2000； Arcury等，2001）。农场工人可用的住房通常位于应用农药的田地附近（住房援助委员会，2001年；早期等，2006），通常不合格，侵扰导致住宅农药施用（Quandt等，2004; Farry等，2006）。农场工人及其配偶通常没有提供保护自己及其家人免于暴露所需的信息（Arcury等，1999； Rao等，2006）。农药暴露的有效剂量显然取决于最初的环境暴露，但也受个人的代谢能力代谢和排泄毒素的影响。 OP农药的代谢主要取决于细胞色素P450家族中的特异性蛋白质和分子的二氧氧蛋白酶类别。这些基因中的几个聚集在同一染色体区域中，表明潜在的常见调节机制，这些机制可能是由这些基因内部或这些基因之间的遗传变异介导的。据报道，PON1中的多态性与PON1酶的水平相关（例如（Holland等，2006）），这表明遗传变异有助于该酶的水平或活性。对于识别单个单个核苷酸多态性（SNP）或SNP的组合，对整个含有PON1，PON2和PON3的PON基因座进行的全面分析是必要的。有人提出，较低的PON1活性导致OP暴露损害影响的风险增加。这项研究的目的是彻底表征参与OP代谢的特定P450基因和整个PON基因座的遗传变异，以识别那些对慢性有机磷酸盐暴露的负面影响影响最大的人。农药暴露是环境健康问题，急性和慢性风险对农场工人来说是一个问题。任何给定个人的风险都可以表示是暴露本身的数量与个人能够代谢和排毒农药的速度之间的相互作用。为了充分了解农药暴露与行为或环境因素之间的联系，分析必须能够考虑农药代谢中的遗传变异性。这项研究的目的是评估北卡罗来纳州农业工人人群中农药代谢的遗传贡献，以便对长期慢性农药暴露的长期影响的潜力有了更全面的了解。