Gene-environment interactions in the development of complex disease phenotypes.
Gene-environment interactions in the development of complex disease phenotypes.
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DOI：
10.3390/ijerph5010004
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发表时间：
2008-03-01
影响因子：
--
通讯作者：
Olden, Kenneth
中科院分区：
文献类型：
--
作者：
Ramos, Rosemarie G;Olden, Kenneth
对疾病发展的最早期事件缺乏了解是由于疾病风险的多因素性质。造成这种信息差距的原因是，人们没有认识到，大多数疾病是由于基因与环境之间的复杂相互作用而产生的，而这种相互作用是个人年龄或发育阶段的一个函数。环境暴露是否会导致疾病取决于所谓的“环境反应机制”的效率（即，可以调节对环境扰动的反应的代谢途径的复合体）。因此，阐明大多数慢性疾病的原因将需要了解遗传和环境对其病因学的贡献。不幸的是，由于对人类基因组的了解有限，以及科学家倾向于使用考虑暴露于单一环境因子的实验模型来研究疾病发展，过去对基因与环境之间关系的探索一直受到阻碍。在过去，在人类疾病病因学研究中很少考虑多个基因之间或基因与环境因子之间的相互作用。最关键的问题是如何将疾病关联研究与途径和机制联系起来。为了了解基因和环境因素如何相互作用，干扰生物途径，导致损伤或疾病，科学家需要能够同时监测数千个基因、蛋白质和代谢物的全球表达的工具。在多个物种中产生这样的数据可用于鉴定涉及基因-环境相互作用的保守的和功能上重要的基因和途径。最终，正是这些知识将用于指导美国卫生与公众服务部等机构在生物医学研究资金和政策方面的决策。
The lack of knowledge about the earliest events in disease development is due to the multi-factorial nature of disease risk. This information gap is the consequence of the lack of appreciation for the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called "environmental response machinery" (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations) that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using experimental models that consider exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies of human disease etiology. The most critical issue is how to relate exposure-disease association studies to pathways and mechanisms. To understand how genes and environmental factors interact to perturb biological pathways to cause injury or disease, scientists will need tools with the capacity to monitor the global expression of thousands of genes, proteins and metabolites simultaneously. The generation of such data in multiple species can be used to identify conserved and functionally significant genes and pathways involved in gene-environment interactions. Ultimately, it is this knowledge that will be used to guide agencies such as the U.S. Department of Health and Human Services in decisions regarding biomedical research funding and policy.