a Université Lille Nord de France , Lille , France.
J Toxicol Environ Health A. 2013;76(15):895-906. doi: 10.1080/15287394.2013.824843.
Lead (Pb) body burden and toxicity may be influenced by genetic polymorphisms. The aim of this study was to investigate the influence of G177C delta-aminolevulinic acid dehydratase (ALAD) polymorphism (rs1800435) on selected Pb exposure biomarkers in a population of workers highly exposed to this metal in the past. A cross-sectional survey was conducted between 2007 and 2009 within the cohort of ex-employees of a smelter in the north of France that closed down in 2003. A questionnaire was completed by each participant and blood samples enabled determination of Pb levels and ALAD polymorphism. Five parameters estimating the Pb body burden and its variations were studied: last blood lead level (BLL) during activity, cumulative blood Pb index, BLL at the time of the study, and absolute and percent changes in BLL after cessation of metal exposure. Multiple regression models were used to evaluate links between ALAD polymorphism and the selected Pb exposure biomarkers. Two hundred and four men were included. At the time of inclusion, the median age was 53.5 yr. The median duration of Pb exposure was 25 yr and the median latency since end of exposure was 5.6 yr. The frequency of ALAD-2 allele was 9.3%, with 34 subjects being heterozygous (ALAD1-2) and 2 homozygous (ALAD2-2). According to genotype, there was no significant difference for any of the five selected Pb exposure biomarkers. These results lend support to the notion that ALAD polymorphism exerts no marked impact on Pb body burden.
铅(Pb)体内负荷和毒性可能受遗传多态性影响。本研究旨在调查 δ-氨基-γ-酮戊酸脱水酶(ALAD)基因 G177C 多态性(rs1800435)对过去曾大量接触该金属的工人中某些 Pb 暴露生物标志物的影响。2007 年至 2009 年期间,在法国北部一家冶炼厂的前员工队列中进行了一项横断面调查。每位参与者填写了一份问卷,并采集了血样,以确定 Pb 水平和 ALAD 多态性。研究了五个估计 Pb 体内负荷及其变化的参数:活动期间的最后一次血铅水平(BLL)、累积血 Pb 指数、研究时的 BLL 以及金属暴露停止后 BLL 的绝对和百分比变化。采用多元回归模型评估了 ALAD 多态性与所选 Pb 暴露生物标志物之间的联系。共纳入 204 名男性。纳入时的中位年龄为 53.5 岁。中位 Pb 暴露时间为 25 年,暴露结束后的中位潜伏期为 5.6 年。ALAD-2 等位基因的频率为 9.3%,34 名受试者为杂合子(ALAD1-2),2 名受试者为纯合子(ALAD2-2)。根据基因型,五个所选 Pb 暴露生物标志物中没有一个存在显著差异。这些结果支持了这样一种观点,即 ALAD 多态性对 Pb 体内负荷没有显著影响。