Department of Pharmacology and Therapeutics, McGill University, Montréimeal, QC.
Allergy Asthma Clin Immunol. 2008 Mar 15;4(1):37-49. doi: 10.1186/1710-1492-4-1-37.
: The long-term effects of behaviour and environmental exposures, particularly during childhood, on health outcomes are well documented. Particularly thought provoking is the notion that exposures to different social environments have a long-lasting impact on human physical health. However, the mechanisms mediating the effects of the environment are still unclear. In the last decade, the main focus of attention was the genome, and interindividual genetic polymorphisms were sought after as the principal basis for susceptibility to disease. However, it is becoming clear that recent dramatic increases in the incidence of certain human pathologies, such as asthma and type 2 diabetes, cannot be explained just on the basis of a genetic drift. It is therefore extremely important to unravel the molecular links between the "environmental" exposure, which is believed to be behind this emerging incidence in certain human pathologies, and the disease's molecular mechanisms. Although it is clear that most human pathologies involve long-term changes in gene function, these might be caused by mechanisms other than changes in the deoxyribonucleic acid (DNA) sequence. The genome is programmed by the epigenome, which is composed of chromatin and a covalent modification of DNA by methylation. It is postulated here that "epigenetic" mechanisms mediate the effects of behavioural and environmental exposures early in life, as well as lifelong environmental exposures and the susceptibility to disease later in life. In contrast to genetic sequence differences, epigenetic aberrations are potentially reversible, raising the hope for interventions that will be able to reverse deleterious epigenetic programming.
行为和环境暴露，特别是在儿童时期，对健康结果的长期影响已得到充分证明。特别引人深思的是，不同的社会环境暴露对人类身体健康有持久影响的观点。然而，介导环境影响的机制仍不清楚。在过去的十年中，人们的主要关注点是基因组，并寻找个体间遗传多态性作为疾病易感性的主要基础。然而，越来越明显的是，某些人类病理（如哮喘和 2 型糖尿病）的发病率最近急剧上升，不能仅仅基于遗传漂移来解释。因此，揭示“环境”暴露与某些人类病理的发病机制之间的分子联系极其重要。尽管很明显，大多数人类病理都涉及基因功能的长期变化，但这些变化可能不是由脱氧核糖核酸（DNA）序列变化引起的。基因组由表观基因组编程，它由染色质和 DNA 的甲基化共价修饰组成。这里推测“表观遗传”机制介导了生命早期的行为和环境暴露以及生命后期的终身环境暴露和对疾病的易感性的影响。与遗传序列差异相反，表观遗传异常具有潜在的可逆性，这增加了干预的希望，即能够逆转有害的表观遗传编程。
