• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >CYP2D6 polymorphisms and pesticide exposure in Parkinson's disease.
【24h】

CYP2D6 polymorphisms and pesticide exposure in Parkinson's disease.

机译：帕金森病患者CYP2D6基因多态性与农药暴露的关系

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The objective of this dissertation was to develop and examine new methods to estimate gene-environment interaction (GEI) effects in disease etiology using Parkinson's disease (PD) as a model. We conducted a case-only study of GEI effects in PD, evaluated the reproducibility of a published CYP2D6 assay and designed a novel CYP2D6 assay for use with buccal DNA, and, designed a simulation study to determine the relative accuracy of case-only and case-control risk estimates of GEI.; In a case-only study of 21 Caucasian PD patients, we examined interaction effects of pesticide exposure and functional polymorphisms in the CYP2D6 gene associated with defective pesticide metabolism in 7–10% of Caucasians. Exposure was ascertained via a questionnaire administered in personal interviews, at which time self-collected DNA samples were obtained from patients using buccal swabs. Several subjects reported pesticide exposure; however, no CYP2D6 poor metabolizers (PM) were identified, thus GEI evaluation was not possible. However, using two historical control groups with characteristics similar to our subjects, we found a statistically significant association between gardening and PD (OR = 5.83, 95% CI 1.70, 21.93) and an increased but not statistically significant risk for ever versus never pesticide exposure (OR combined = 1.52, 95% CI 0.50, 4.46; ORControlGroup1 = 1.39, 95% CI 0.43, 4.33; ORControlGroup2 = 1.67, 95% CI 0.51, 5.24).; We demonstrated failure of a published polymerase chain reaction (PCR) assay for simultaneous detection of five most common CYP2D6 PM alleles in Caucasians to produce results using a non-blood source of DNA and designed a new PCR assay for use with buccal cells to simultaneously detect CYP2D6*4 and *5, the two most common PM alleles in Caucasians.; We compared accuracy of case-only and case-control risk estimates of Type 2 GEI effects in a simulation study using populations with known risks. Case-only estimates were shown to approximate known risks more consistently and accurately under most conditions provided gene and exposure of interest are independent in the population. We demonstrated the influence of sample size on accuracy of both estimates, and showed that inadequate study size can lead to such large random error as to result in inaccurate estimates despite efforts to eliminate bias.
机译：本文的目的是开发和检验以帕金森氏病（PD）为模型估算基因-环境相互作用（GEI）在疾病病因中的作用的新方法。我们对GEI在PD中的作用进行了仅案例研究，评估了已发表的CYP2D6测定法的可重复性，并设计了一种用于颊DNA的新型CYP2D6测定法，并设计了模拟研究以确定仅病例与病例的相对准确性-控制GEI的风险估计；在一项针对21名高加索PD患者的个案研究中，我们研究了7-10％的高加索人中农药暴露与CYP2D6基因功能多态性与农药代谢缺陷相关的相互作用。通过在个人访谈中进行的问卷调查确定暴露程度，这时使用口腔拭子从患者身上收集自我收集的DNA样本。一些受试者报告了农药暴露；然而，没有发现CYP2D6弱代谢者（PM），因此无法进行GEI评估。但是，使用两个历史对照组，其特征与我们的受试者相似，我们发现园艺和PD之间存在统计学上的显着相关性（OR = 5.83，95％CI 1.70，21.93），而且从未接触过或从未接触过农药的风险增加但无统计学意义（OR 合并 = 1.52，95％CI 0.50，4.46； OR ControlGroup1 = 1.39，95％CI 0.43，4.33； OR ControlGroup2 = 1.67 ，95％CI 0.51，5.24）。我们证明了已发表的聚合酶链反应（PCR）测定法无法同时检测高加索人中五个最常见的CYP2D6 PM等位基因，无法使用非血液来源的DNA产生结果，并且设计了一种新的PCR测定法与颊细胞同时检测CYP2D6 * 4和* 5，是白种人中最常见的两个PM等位基因。在一项使用已知风险人群的模拟研究中，我们比较了第2类GEI效应的仅病例和病例对照风险估计的准确性。只要基因和目标人群在人群中是独立的，在大多数情况下，仅病例估计值就能更一致，更准确地估算已知风险。我们证明了样本量对这两种估计的准确性的影响，并表明研究规模不足会导致如此大的随机误差，从而尽管消除了偏差仍会导致估计不准确。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号