MOLECULAR GENETICS OF ESSENTIAL HYPERTENSION

高血压影响着每5个澳大利亚成年人中的1个，是心脏病发作和中风导致死亡和发病的主要原因。这种情况往往在家族中发生，面对环境因素，遗传易感性会导致血压升高。我的实验室已经证明了我们收集的受影响的高血压同胞队列的能力，以在达到全基因组统计意义的水平上找到原发性高血压的基因座，并已发表在领先的分子遗传学杂志上。此外，这项先前的工作，包括在扫描1号染色体后找到一个提示基因的精细定位，不仅证明了显著的联系，而且还继续比较了有两个患病父母的(无关的)高血压受试者的不同队列中的基因标记，以及父母未受影响的血压正常的匹配受试者之间的基因标记物，以确定可能的候选基因。同样的方法将被用来完成基因组的其余部分。高血压所有基因的发现将是：(1)开发新的、更有效的治疗方法，因为负责的基因产品将能够被新的治疗方法靶向，(2)对生命早期的个体进行基因分型，以便告知他们他们的风险是什么，从而允许有关改变生活方式的咨询，(3)更合理地根据导致高血压的体积-神经-血管收缩成分来应用现有的治疗策略。

High blood pressure affects 1 in 5 Australian adults and is a leading cause of mortality and morbidity from heart attack and stroke. The condition tends to run in families and genetic predisposition, in the face of environmental factors, leads to the elevation in blood pressure. My Lab has demonstrated the capacity of a cohort of affected hypertensive sibships we have collected to find loci for essential hypertension at a level that has achieved genome-wide statistical significance and has been published in a leading molecular genetics journal. Moreover, this previous work, which included fine-mapping after finding a suggestive locus following a scan of chromosome 1, not only demonstrated significant linkage, but also went on to compare gene markers between a different cohort of (unrelated) hypertensive subjects with 2 affected parents (and early-onset, moderate to severe hypertension) and control normotensive matched subjects with unaffected parents, to identify a likely candidate gene. This same approach will be used to complete the rest of the genome. The discovery of all of the genes for essential hypertension will be an important prelude to: (1) developing new, more effective treatments, since the gene products responsible will be able to be targetted by novel therapeutics, (2) genotyping individuals early in life in order to advise them what their risk is, and thus allow couselling about lifestyle modification, (3) more logically apply existing treatment strategies according to the volume-neural-vasoconstrctor component of the contribution to high blood pressure.