Zaiou M, El Amri H
Faculté de Pharmacie, Université de Lorraine, Nancy, France.
Laboratoire de Génétique de la Gendarmerie Royale, Avenue Ibn Sina, Rabat, Maroc.
Clin Genet. 2017 Mar;91(3):355-370. doi: 10.1111/cge.12881. Epub 2016 Nov 30.
Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high-throughput genetics and genomics technology and newer genome-wide study approaches, a number of genetic variations across the human genome were uncovered. Evidence suggests that genetic defects could influence CVD development and inter-individual responses to widely used cardiovascular drugs like clopidogrel, aspirin, warfarin, and statins, and therefore, they may be integrated into clinical practice. If clinically validated, better understanding of these genetic variations may provide new opportunities for personalized diagnostic, pharmacogenetic-based drug selection and best treatment in personalized medicine. However, numerous gaps remain unsolved due to the lack of underlying pathological mechanisms for how genetic predisposition could contribute to CVD. This review provides an overview of the extraordinary scientific progress in our understanding of genetic and genomic basis of CVD as well as the development of relevant genetic biomarkers for this disease. Some of the actual limitations to the promise of these markers and their translation for the benefit of patients will be discussed.
心血管疾病(CVD)是全球主要的死亡原因。CVD的根本原因尚未完全明确。大量证据表明,遗传易感性在这种复杂疾病的病理生理过程中起着至关重要的作用。因此,确定CVD的遗传因素可能会提高诊断准确性,并更好地预测个体风险。随着高通量遗传学和基因组学技术以及更新的全基因组研究方法的出现,人类基因组中发现了许多遗传变异。有证据表明,遗传缺陷可能影响CVD的发展以及个体对氯吡格雷、阿司匹林、华法林和他汀类药物等广泛使用的心血管药物的反应,因此,它们可能会被纳入临床实践。如果经过临床验证,更好地了解这些遗传变异可能为个性化诊断、基于药物遗传学的药物选择以及个性化医疗中的最佳治疗提供新的机会。然而,由于缺乏遗传易感性如何导致CVD的潜在病理机制,许多问题仍未得到解决。本综述概述了我们在理解CVD的遗传和基因组基础以及开发该疾病相关遗传生物标志物方面取得的非凡科学进展。还将讨论这些标志物应用前景及其转化为患者受益的实际局限性。