Dechamethakun Sariya, Muramatsu Masaaki
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
J Hum Genet. 2017 Jan;62(1):97-104. doi: 10.1038/jhg.2016.70. Epub 2016 Jun 16.
Cardiometabolic diseases are characterized as a combination of multiple risk factors for cardiovascular disease (CVD) and metabolic diseases including diabetes mellitus, dyslipidemia, hypertension and abdominal obesity. This cluster of abnormalities individually and interdependently leads to atherosclerosis and CVD morbidity and mortality. In the past decade, genome-wide association studies (GWASs) have identified a series of cardiometabolic disease-associated variants that can collectively explain a small proportion of the variability. Intriguingly, the susceptibility variants imputed from GWASs usually do not reside in the coding regions, suggesting a crucial role of the noncoding elements of the genome. In recent years, emerging evidence suggests that noncoding RNA (ncRNA) is functional for physiology and pathophysiology of human diseases. These include microRNAs and long noncoding RNAs (lncRNAs) that are now implicated in human diseases. The ncRNAs can interact with each other and with proteins, to interfere gene expressions, leading to the development of many human disorders. Although evidence suggests the functional role of lncRNAs in cardiometabolic traits, the molecular mechanisms of gene regulation underlying cardiometabolic diseases remain to be better defined. Here, we summarize the recent discoveries of lncRNA variations in the context of cardiometabolic diseases.
心脏代谢疾病的特征是心血管疾病(CVD)和代谢疾病(包括糖尿病、血脂异常、高血压和腹型肥胖)的多种风险因素并存。这一系列异常单独或相互依赖地导致动脉粥样硬化以及CVD的发病和死亡。在过去十年中,全基因组关联研究(GWAS)已经鉴定出一系列与心脏代谢疾病相关的变异,这些变异共同只能解释一小部分变异性。有趣的是,从GWAS中推断出的易感性变异通常并不位于编码区,这表明基因组非编码元件起着关键作用。近年来,新出现的证据表明非编码RNA(ncRNA)在人类疾病的生理和病理生理过程中具有功能。这些包括现在与人类疾病有关的微小RNA和长链非编码RNA(lncRNA)。ncRNA可以相互作用并与蛋白质相互作用,干扰基因表达,导致许多人类疾病的发生。虽然有证据表明lncRNA在心脏代谢特征中具有功能作用,但心脏代谢疾病潜在的基因调控分子机制仍有待进一步明确。在此,我们总结了在心脏代谢疾病背景下lncRNA变异的最新发现。