Department of Ophthalmology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Adv Exp Med Biol. 2021;1256:221-235. doi: 10.1007/978-3-030-66014-7_9.
Aberrant regulation of epigenetic mechanisms, including the two most common types; DNA methylation and histone modification have been implicated in common chronic progressive conditions, including Alzheimer disease, cardiovascular disease, and age-related macular degeneration (AMD). All these conditions are complex, meaning that environmental factors, genetic factors, and their interactions play a role in disease pathophysiology. Although genome wide association studies (GWAS), and studies on twins demonstrate the genetic/hereditary component to these complex diseases, including AMD, this contribution is much less than 100%. Moreover, the contribution of the hereditary component decreases in the advanced, later onset forms of these chronic diseases including AMD. This underscores the need to elucidate how the genetic and environmental factors function to exert their influence on disease pathophysiology. By teasing out epigenetic mechanisms and how they exert their influence on AMD, therapeutic targets can be tailored to prevent and/or slow down disease progression. Epigenetic studies that incorporate well-characterized patient tissue samples (including affected tissues and peripheral blood), similar to those relevant to gene expression studies, along with genetic and epidemiological information, can be the first step in developing appropriate functional assays to validate findings and identify potential therapies.
表观遗传机制的异常调节，包括最常见的两种类型；DNA 甲基化和组蛋白修饰，与常见的慢性进行性疾病有关，包括阿尔茨海默病、心血管疾病和年龄相关性黄斑变性（AMD）。所有这些疾病都是复杂的，这意味着环境因素、遗传因素及其相互作用在疾病的病理生理学中起作用。尽管全基因组关联研究（GWAS）和双胞胎研究表明，包括 AMD 在内的这些复杂疾病具有遗传/遗传性成分，但这一贡献不到 100%。此外，遗传成分在这些慢性疾病的晚期、发病较晚的形式中，如 AMD，其贡献会减少。这突显出需要阐明遗传和环境因素如何发挥作用，对疾病的病理生理学产生影响。通过梳理表观遗传机制及其对 AMD 的影响，可以针对治疗靶点进行定制，以预防和/或减缓疾病进展。纳入经过良好特征描述的患者组织样本（包括受影响的组织和外周血）的表观遗传学研究，类似于与基因表达研究相关的样本，以及遗传和流行病学信息，可以作为开发适当的功能测定以验证发现并确定潜在治疗方法的第一步。
