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与健康相关的差异:环境因素的影响

Health-related disparities: influence of environmental factors.

作者信息

Olden Kenneth, White Sandra L

机构信息

National Institute of Environmental Health Sciences, United States Department of Health and Human Services, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA.

出版信息

Med Clin North Am. 2005 Jul;89(4):721-38. doi: 10.1016/j.mcna.2005.02.001.

DOI:10.1016/j.mcna.2005.02.001
PMID:15925646
Abstract

Racial disparities in health cannot be explained solely on the basis of poverty, access to health care, behavior, or environmental factors. Their complex etiology is dependent on interactions between all these factors plus genetics. Scientists have been slow to consider genetics as a risk factor because genetic polymorphisms tend to be more variable within a race than between races. Now that studies are demonstrating the existence of racial differences in allelic frequencies for multiple genes affecting a single biologic mechanism, the present argument for a significant genetic role in contributing to health disparities is gaining support. Individuals vary, often significantly, in their response to environmental agents. This variability provides a high "background noise" when scientists examine human populations to identify environmental links to disease. This variability often masks important environmental contributors to disease risk and is a major impediment to efforts to investigate the causes of diseases.Fortunately, investments in the various genome projects have led to the development of tools and databases that can be used to help identify the genetic variations in environmental response genes that can lead to such wide differences in disease susceptibility. NIEHS developed the environ-mental genome project to catalog these genetic variants (polymorphisms)and to identify the ones that play a major role in human susceptibility to environmental agents. This information is being used in epidemiologic studies to pinpoint environmental contributors to disease better. The research summarized in this article is critically important for tying genetics and the environment to health disparities, and for the development of a rational approach to gauge environmental threats. Common variants in genes play pivotal roles in determining if or when illness or death result from exposure to drugs or environmental xenobiotics. Most common variants exist in all human populations, but their frequency can vary substantially,rendering individuals or groups more or less susceptible to particular environmental exposures. Such findings are consistent with the highly publicized analogy, "genetics loads the gun, but the environment pulls the trigger." That is, one can inherit the genetic predisposition to develop a disease but will do so only if or when exposed to the environmental trigger. Poor people have approximately the same genetic makeup as everyone else,but they have the unfortunate experience of living and working in environments containing multiple and high levels of carcinogens or other toxicants capable of interacting with susceptibility genes to cause disease.Furthermore, certain disadvantaged ethnic groups may have a higher incidence of certain susceptible genes that render them more vulnerable to adverse effects of the environments they inhabit. For both of these reasons,much of the nation's disease burden could likely be reduced through better environmental protection practices, especially in low-income and minority communities. Of the many implications of polymorphisms and frequency variations for public health and the practice of medicine, however, none is more urgent than the choice of drugs in therapy. Using such knowledge,randomized trials have identified race-specific drug response differences between blacks and whites [42].To date, most knowledge of the health effects of environmental factors is derived from studies of single agents. The reality, though, is that environmental contributions to health disparities are mostly from multiple agents. These simultaneous exposures to multiple risk factors, which may accumulate or interact synergistically, remain to be fully explained and defined.Finally, health disparity is a significant public health problem that cannot be solved using "business as usual" approaches for funding and priority setting. The current emphasis on basic and clinical research at the exclusion of public health and the social sciences does not provide the interdisciplinary research teams necessary to address such a complex problem as health disparities. Although the poor will always be with us, their health could be greatly improved if social, environmental, and genetic scientists could find ways to collaborate and develop more insightful and relevant ways to address the health of disadvantaged communities.

摘要

健康方面的种族差异不能仅仅基于贫困、获得医疗保健的机会、行为或环境因素来解释。其复杂的病因取决于所有这些因素以及遗传学之间的相互作用。科学家们一直迟迟没有将遗传学视为一个风险因素,因为基因多态性在一个种族内部往往比在不同种族之间更具变异性。如今,研究表明,影响单一生物学机制的多个基因的等位基因频率存在种族差异,目前关于遗传学在导致健康差异方面发挥重要作用的观点正获得支持。个体对环境因素的反应往往存在很大差异。当科学家们研究人群以确定疾病与环境的关联时,这种变异性产生了很高的“背景噪音”。这种变异性常常掩盖了环境对疾病风险的重要影响因素,并且是调查疾病病因工作的主要障碍。幸运的是,对各种基因组项目的投入已促成了一些工具和数据库的开发,这些工具和数据库可用于帮助识别环境反应基因中的遗传变异,这些变异会导致疾病易感性出现如此大的差异。美国国立环境卫生科学研究所开展了环境基因组项目,以编目这些遗传变异(多态性),并识别那些在人类对环境因素的易感性中起主要作用的变异。这些信息正被用于流行病学研究,以便更好地确定环境对疾病的影响因素。本文总结的研究对于将遗传学和环境与健康差异联系起来,以及制定合理的方法来评估环境威胁至关重要。基因中的常见变异在确定接触药物或环境异源生物是否会导致疾病或何时导致疾病或死亡方面起着关键作用。大多数常见变异存在于所有人群中,但其频率可能有很大差异,这使得个体或群体对特定环境暴露的易感性或多或少有所不同。这些发现与广为宣传的比喻“遗传学装上了枪,但环境扣动了扳机”是一致的。也就是说,一个人可能遗传了患某种疾病的易感性,但只有在接触到环境触发因素时才会发病。穷人的基因构成与其他人大致相同,但他们不幸的是生活和工作在含有多种高浓度致癌物或其他能够与易感基因相互作用导致疾病的毒物的环境中。此外,某些弱势群体中某些易感基因的发生率可能较高,这使他们更容易受到所居住环境的不利影响。出于这两个原因,如果能采取更好的环境保护措施,尤其是在低收入和少数族裔社区,该国的许多疾病负担很可能会减轻。然而,多态性和频率变异对公共卫生和医学实践有诸多影响,其中最紧迫的莫过于治疗中药物的选择。利用这些知识,随机试验已确定黑人和白人之间存在种族特异性的药物反应差异[42]。到目前为止,大多数关于环境因素对健康影响的知识都来自对单一因素的研究。然而,实际情况是,环境对健康差异的影响大多来自多种因素。这些同时接触多种风险因素的情况,可能会累积或产生协同作用,仍有待充分解释和界定。最后,健康差异是一个重大的公共卫生问题,不能用“照常营业”的方式来解决资金和优先事项的设定问题。目前对基础研究和临床研究的重视,而忽视公共卫生和社会科学,无法提供解决像健康差异这样复杂问题所需的跨学科研究团队。虽然穷人将永远存在,但如果社会、环境和遗传科学家能够找到合作方式,并开发出更有见地和相关性更强的方法来解决弱势群体的健康问题,他们的健康状况会得到极大改善。

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