Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy.
Thromb Res. 2012 Mar;129(3):320-4. doi: 10.1016/j.thromres.2011.11.014. Epub 2011 Dec 9.
Continuous updating of the genotyping technology has led to improvement of genetic study design. The recent advances in technology coupled with the advances in our understanding of the molecular mechanisms have allowed a more comprehensive examination of the role of genetics, environment and their interaction in determining the individual risk of cardiovascular disease (CVD). Initial candidate gene studies identified a limited number of polymorphisms associated with disease, explaining only a minor part of trait variance. Furthermore, results were not often concordant, with meta-analyses not reaching the statistical power to confirm an association in many cases. The advent of the genome-wide design furnished an enormous quantity of information and decreased time of genotyping, while increased complexity of analyses and costs. Their results were more concordant, even when they suggested associations between CVD and polymorphisms distant from codifying regions or in genes involved in previously unsuspected pathways. Future results from genome-wide studies coupled with results from functional studies and investigation on gene-environment interactions will allow improvement of cardiovascular risk assessment and discovery of new targets for therapy and prevention. In this review, a brief history of cardiovascular genetics is reported, from candidate gene to genome wide association studies, that led to the identification of association between CVD and SNPs in the 9p21 region, firstly thought a gene desert without importance.
基因分型技术的不断更新导致遗传研究设计的改进。技术的最新进展以及我们对分子机制的理解的提高，使得更全面地研究遗传、环境及其相互作用在确定心血管疾病（CVD）个体风险中的作用成为可能。最初的候选基因研究确定了与疾病相关的少数几种多态性，仅能解释性状变异的一小部分。此外，结果并不总是一致的，荟萃分析在许多情况下都未能达到统计学上确认相关性的功效。全基因组设计的出现提供了大量的信息，减少了基因分型的时间，同时增加了分析的复杂性和成本。它们的结果更加一致，即使它们表明 CVD 与远离编码区域的多态性或参与以前未被怀疑的途径的基因之间存在关联。来自全基因组研究的未来结果，以及功能研究和基因-环境相互作用的结果，将改善心血管风险评估，并发现新的治疗和预防靶点。在这篇综述中，简要回顾了从候选基因到全基因组关联研究的心血管遗传学历史，这些研究导致了在 9p21 区域发现 CVD 与 SNPs 之间的关联，该区域最初被认为是一个没有重要性的基因荒漠。
