阐明与化学暴露易感性差异相关的基因-环境相互作用。
Elucidating Gene-by-Environment Interactions Associated with Differential Susceptibility to Chemical Exposure.
机构信息
Bioinformatics Research Center, Center for Human Health and the Environment, Dept. of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Sinnhuber Aquatic Research Laboratory, Dept. of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA.
出版信息
Environ Health Perspect. 2018 Jun 28;126(6):067010. doi: 10.1289/EHP2662. eCollection 2018 Jun.
BACKGROUND
Modern societies are exposed to vast numbers of potentially hazardous chemicals. Despite demonstrated linkages between chemical exposure and severe health effects, there are limited, often conflicting, data on how adverse health effects of exposure differ across individuals.
OBJECTIVES
We tested the hypothesis that population variability in response to certain chemicals could elucidate a role for gene-environment interactions (GxE) in differential susceptibility.
METHODS
High-throughput screening (HTS) data on thousands of chemicals in genetically heterogeneous zebrafish were leveraged to identify a candidate chemical (Abamectin) with response patterns indicative of population susceptibility differences. We tested the prediction by generating genome-wide sequence data for 276 individual zebrafish displaying susceptible (Affected) vs. resistant (Unaffected) phenotypes following identical chemical exposure.
RESULTS
We found GxE associated with differential susceptibility in the promoter region and then confirmed gene expression differences between phenotypic response classes.
CONCLUSIONS
The results for Abamectin in zebrafish demonstrate that GxE associated with naturally occurring, population genetic variation play a significant role in mediating individual response to chemical exposure. https://doi.org/10.1289/EHP2662.
背景
现代社会暴露于大量潜在有害化学物质中。尽管已经证明化学物质暴露与严重健康影响之间存在关联，但关于暴露对个体的不良健康影响如何存在差异的数据有限，且往往相互矛盾。
目的
我们检验了这样一个假设，即对某些化学物质的人群变异反应可以阐明基因-环境相互作用（GxE）在易感性差异中的作用。
方法
利用遗传异质斑马鱼中数千种化学物质的高通量筛选（HTS）数据，确定了一种候选化学物质（阿维菌素），其反应模式表明存在人群易感性差异。我们通过生成 276 条个体斑马鱼的全基因组序列数据来测试这一预测，这些斑马鱼在接受相同的化学暴露后表现出易感（受影响）和抗药（未受影响）表型。
结果
我们发现 GxE 与 启动子区域的易感性差异相关，然后证实了表型反应类别之间的基因表达差异。
结论
阿维菌素在斑马鱼中的结果表明，与自然发生的、种群遗传变异相关的 GxE 在介导个体对化学物质暴露的反应方面起着重要作用。https://doi.org/10.1289/EHP2662.
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