Environmental and Genetic Epidemiology Research Group, Public Health Genes and Environment Theme, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia.
Pediatr Res. 2013 Apr;73(4 Pt 2):523-30. doi: 10.1038/pr.2013.6. Epub 2013 Jan 11.
Cardiovascular disease (CVD) is the leading cause of death worldwide and originates in early life. The exact mechanisms of this early-life origin are unclear, but a likely mediator at the molecular level is epigenetic dysregulation of gene expression. Epigenetic factors have thus been posited as the likely drivers of early-life programming of adult-onset diseases. This review summarizes recent advances in epidemiology and epigenetic research of CVD risk in children, with a particular focus on twin studies. Classic twin studies enable partitioning of phenotypic variance within a population into additive genetic, shared, and nonshared environmental variances, and are invaluable in research in this area. Longitudinal cohort twin studies, in particular, may provide important insights into the role of epigenetics in the pathogenesis of CVD. We describe candidate gene and epigenome-wide association studies (EWASs) and transgenerational epigenetic inheritance of CVD, and discuss the potential for evidence-based interventions. Identifying epigenetic changes associated with CVD-risk biomarkers in children will provide new opportunities to unravel the underlying biological mechanism of the origins of CVD and enable identification of those at risk for early-life interventions to alter the risk trajectory and potentially reduce CVD incidence later in life.
心血管疾病 (CVD) 是全球范围内的主要死亡原因，起源于生命早期。这种生命早期起源的确切机制尚不清楚，但分子水平上的一个可能的中介物是基因表达的表观遗传失调。因此，表观遗传因素被认为是导致成年期疾病早期发生的潜在驱动因素。本综述总结了儿童 CVD 风险的流行病学和表观遗传研究的最新进展，特别关注双胞胎研究。经典的双胞胎研究使人群内表型变异可以分为加性遗传、共享和非共享环境变异，这在该领域的研究中非常有价值。特别是纵向队列双胞胎研究，可能为 CVD 发病机制中的表观遗传学作用提供重要见解。我们描述了候选基因和全基因组关联研究 (EWAS) 以及 CVD 的跨代表观遗传遗传，并讨论了基于证据的干预措施的潜力。确定与儿童 CVD 风险生物标志物相关的表观遗传变化将为揭示 CVD 起源的潜在生物学机制提供新的机会，并能够识别那些存在风险的人，以便进行早期生活干预来改变风险轨迹，并有可能降低日后 CVD 的发病率。
