对氧磷酶的遗传学和表观遗传学研究进展：为何其与儿童环境卫生相关
Recent progress in the genetics and epigenetics of paraoxonase: why it is relevant to children's environmental health.
作者信息
Holland Nina, Lizarraga Daneida, Huen Karen
机构信息
Environmental Health Sciences Division and the Center for Environmental Research and Children's Health, School of Public Health, University of California, Berkeley, California, USA.
出版信息
Curr Opin Pediatr. 2015 Apr;27(2):240-7. doi: 10.1097/MOP.0000000000000192.
PURPOSE OF REVIEW
Children are more susceptible to exposures in utero and during early childhood that may result in developmental problems and chronic diseases. Novel discoveries in the field of molecular epidemiology that can help explain susceptibility to exposures and disease will be demonstrated using the multifunctional enzyme paraoxonase 1 (PON1) as an example.
RECENT FINDINGS
The broad PON1 variability in humans, partly due to differences in genetics and age, can confer differential susceptibility because this enzyme can detoxify organophosphate pesticides and has antioxidant properties. Epigenetics plays a significant role in the mediation of the effects of environmental exposure on human health and is hypothesized to be a major contributing factor to the early-life origins of adult disease. Studies highlighted in this review demonstrate the relationship of PON1 polymorphisms with microRNA binding in addition to a link between DNA methylation in the transcriptional regulatory region with changes in PON1 enzyme levels. Other important methodologies such as ancestry informative markers and lactonase activity can enhance studies involving PON1.
SUMMARY
This PON1 model demonstrates that integrating genetic and epigenetic factors, as well as other novel methodologies, can improve our understanding of important susceptibility factors linked to pediatric disease.
综述目的
儿童在子宫内和幼儿期更容易受到可能导致发育问题和慢性疾病的暴露影响。本文将以多功能酶对氧磷酶1（PON1）为例，展示分子流行病学领域中有助于解释暴露易感性和疾病的新发现。
最新研究成果
人类PON1存在广泛变异，部分原因是基因和年龄差异，这种酶能够解毒有机磷农药并具有抗氧化特性，因此这种变异会导致不同的易感性。表观遗传学在介导环境暴露对人类健康的影响中起重要作用，并且被认为是成人疾病早期起源的主要促成因素。本综述中强调的研究表明，PON1多态性与微小RNA结合之间存在关系，此外转录调控区域的DNA甲基化与PON1酶水平变化之间也存在联系。其他重要方法，如祖先信息标记和内酯酶活性，可加强涉及PON1的研究。
总结
这个PON1模型表明，整合遗传和表观遗传因素以及其他新方法，可以增进我们对与儿科疾病相关的重要易感性因素的理解。
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