Rodríguez Alejandra, Pajukanta Päivi
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, USA.
Molecular Biology Institute, University of California, Los Angeles, USA.
Rev Invest Clin. 2018;70(5):217-223. doi: 10.24875/RIC.18002576.
Cardiovascular disease (CVD) is a broad definition for diseases of the heart and blood vessels with high mortality and morbidity worldwide. Atherosclerosis and hypertension are the most common causes of CVD, and multiple factors confer the susceptibility. Some of the predisposing factors are modifiable such as diet, smoking, and exercise, whereas others, including age, sex, and individual's genetic variations contributing to the CVD composition traits, are non-modifiable. This latter group includes serum lipid traits. High serum lipid levels, specifically high levels of serum low-density lipoprotein cholesterol and triglycerides, are well-established key risk factors of atherosclerosis. This review will discuss genomics and systems biology approaches in the study of common dyslipidemias. The non-Mendelian forms of dyslipidemias are highly complex, and the molecular mechanisms underlying these polygenic lipid disorders are estimated to involve hundreds of genes. Interactions between the different genes and environmental factors also contribute to the clinical outcomes; however, very little is known about these interactions and their molecular mechanisms. To better address the complex genetic architecture and multiple properties leading to high serum lipid levels, networks and systems approach combining information at genomic, transcriptomics, methylomics, proteomics, metabolomics, and phenome level are being developed, with the ultimate goal to elucidate the cascade of dynamic changes leading to CVD in humans. (REV INVEST CLIN. 2018;70:217-23).
心血管疾病（CVD）是一个广泛的定义，指的是心脏和血管疾病，在全球范围内具有高死亡率和高发病率。动脉粥样硬化和高血压是心血管疾病最常见的病因，多种因素导致易感性。一些诱发因素是可改变的，如饮食、吸烟和运动，而其他因素，包括年龄、性别以及导致心血管疾病构成特征的个体基因变异，则是不可改变的。后一组因素包括血脂特征。高血清脂质水平，特别是高血清低密度脂蛋白胆固醇和甘油三酯水平，是公认的动脉粥样硬化关键危险因素。本综述将讨论常见血脂异常研究中的基因组学和系统生物学方法。非孟德尔形式的血脂异常非常复杂，这些多基因脂质紊乱的分子机制估计涉及数百个基因。不同基因与环境因素之间的相互作用也会影响临床结果；然而，对于这些相互作用及其分子机制知之甚少。为了更好地解决导致高血清脂质水平的复杂遗传结构和多种特性，正在开发结合基因组、转录组、甲基组、蛋白质组、代谢组和表型水平信息的网络和系统方法，最终目标是阐明导致人类心血管疾病的动态变化级联。（《临床研究回顾》。2018年；70:217 - 23）
