概要
　　遗传学在罕见疾病管理中的作用
　　在罕见疾病领域目前有一些进展。在过去，谈到罕见的单基因遗传的高血压病或符合孟德尔遗传规律的疾病，是指一个基因突变导致疾病发生。尽管这种单基因遗传病非常罕见。但对高血压专科医生而言在其整个职业生涯中可能会遇到这样的家系。在过去的几年中，我们开始把一些所谓的散发性高血压归因到不同的已知基因组和家系中，例如原发性醛固酮增多症和嗜铬细胞瘤。在这些疾病，我们越来越能体会到遗传学所带来的帮助。不同基因型代表了不同的风险，决定了患者的随访和管理有所不同。例如，10%的嗜铬细胞瘤和20%的副神经节瘤是恶性的，患者的生存率低，如果一位副神经节瘤患者有SDHB基因突变，那么其恶性的可能性会达50%，遗传学检查有助于我们预测这些患者的转归，这显然这也是患者和家属想要了解的事情。
　　遗传学在高血压管理中的作用
　　我们对疾病的理解变得越来越精细，这也是我们所期望的。最近美国一个研究小组在科学杂志发表了一篇关于Conn综合征发病机制的论文。其中描述了一种新的基因突变-KCNJ5突变，这种突变与盐分泌有关有关，它能进入细胞膜并导致细胞增生。任何疾病都有其相应的发病机制，药物的开发与疾病的发病机制有关。只有更好地理解疾病发病机制才能够开发出更好的新药，进行更好地治疗。我们不仅想借助遗传学治疗一些罕见疾病，同时也想应用于心脏病、糖尿病和癌症等慢性疾病的治疗上。如在高血压治疗领域，由于高血压不只一种，对于每一个高血压患者而言都有其自身特点。但是目前我们还没有对高血压患者进行系统分组，而这正是遗传学将要进行的事。我们不必对与高血压相关的所有基因都了如指掌。但是我们需要一些基因指纹，从而可以对高血压人群进行分组，使患者能够从不同的单药或联合治疗中获益。

　　International Circulation: You are giving a presentation entitled “How Useful was the Discovery of the Human Genome for the Management of Hypertension?” How much will your talk be focusing on rare syndromes?
　　Prof. Dominiczak: While we are talking about rare disorders， there has been some progress. We used to talk about the rare monogenic forms of hypertension， the Mendelian forms where there is one gene that explains the entire disease. Those are very rare. A doctor who specializes in hypertension may see one of these families in a lifetime. In the last few years， though， researchers have started breaking down sporadic forms of hypertension into known gene groups and families. These are uncommon disorders such as hyperaldosteronism or pheochromocytoma， but not as rare as those monogenic ones. In a specialist center， we might see one hundred individuals a year with these sporadic forms. In these cases， we increasingly see that genetics helps. There is sometimes a necessity to screen the family. And for the individual affected， some of the genetics may tell you there is much higher preponderance of malignancy. The risk is different， the follow-up of patients is different， and the management is different. 10% of pheochromocytomas and 20% of paragangliomas are malignant with poor survival. Paragangliomas related to an SDHB mutation， though， have a 50% malignancy rate. Genetic testing helps to predict what is going to happen， which obviously the patient and their families will want to know.
　　International Circulation: How else is knowledge of genetics changing our approach to these kinds of disorders?
　　Prof. Dominiczak: Our understanding of disorders is getting more and more complicated and we love complicated. Just recently a fantastic American group published a paper in Science looking into the mechanisms of Conn’s Syndrome. They described a new mutation， KCNJ5， that has everything to do with sodium， how it crosses a membrane， and how cells grow. It is a completely new mechanism for a disease that we thought came from nowhere. But nothing comes from nowhere in medicine. There is always a mechanism.
　　This is the direction we are moving. You always treat diseases better if you understand the mechanism. The way to make new drugs and make better treatments is only through better understanding of the mechanism. It rarely happens by guessing. Genetics wants to transform not just the treatment of these rare conditions， but the common chronic diseases such as heart disease， diabetes， cancer. That is the Holy Grail. I think the big thing for the future is stratified medicine. Not everybody is the same in that big group of millions of people with hypertension. There is not just one hypertension. We just have not systematically divided everybody into the subgroups. That is what genetics is going to do. We do not necessarily need to understand and know by heart every gene of the hundred or two hundred that contribute to high blood pressure in the general population， but we need to have some signatures to stratify the huge number of patients into those who benefit from this group of drugs or that group of drugs， or probably this or that combination.