Delles Christian, McBride Martin W, Graham Delyth, Padmanabhan Sandosh, Dominiczak Anna F
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK.
Biochim Biophys Acta. 2010 Dec;1802(12):1299-308. doi: 10.1016/j.bbadis.2009.12.006. Epub 2009 Dec 24.
Essential hypertension affects 20 to 30% of the population worldwide and contributes significantly to cardiovascular mortality and morbidity. Heridability of blood pressure is around 15 to 40% but there are also substantial environmental factors affecting blood pressure variability. It is assumed that blood pressure is under the control of a large number of genes each of which has only relatively mild effects. It has therefore been difficult to discover the genes that contribute to blood pressure variation using traditional approaches including candidate gene studies and linkage studies. Animal models of hypertension, particularly in the rat, have led to the discovery of quantitative trait loci harbouring one or several hypertension related genes, but translation of these findings into human essential hypertension remains challenging. Recent development of genotyping technology made large scale genome-wide association studies possible. This approach and the study of monogenic forms of hypertension has led to the discovery of novel and robust candidate genes for human essential hypertension, many of which require functional analysis in experimental models.
原发性高血压影响着全球20%至30%的人口,并对心血管疾病的死亡率和发病率有显著影响。血压的遗传度约为15%至40%,但也有大量环境因素影响血压变异性。据推测,血压受大量基因控制,每个基因的影响相对较小。因此,使用包括候选基因研究和连锁研究在内的传统方法很难发现导致血压变化的基因。高血压动物模型,尤其是大鼠模型,已促使人们发现了含有一个或几个高血压相关基因的数量性状基因座,但将这些发现转化为人类原发性高血压仍具有挑战性。基因分型技术的最新发展使大规模全基因组关联研究成为可能。这种方法以及对单基因形式高血压的研究已促使人们发现了用于人类原发性高血压的新的、可靠的候选基因,其中许多基因需要在实验模型中进行功能分析。