International Circulation:  What is the role of genetic variations in the development of hypertension?
Prof. Daniel T. O’Connor:  This is an area of ongoing investigation.  It looks as if probably the best evidence that we can marshal is family studies either pedigree studies or twin studies or relative risk studies – sibling studies.  And it looks like about half or so of the variation in blood pressure that we see in the population is the result of gene action.  We call this the concept of inheritability.  So blood pressure in general and hypertension in particular seem to be heritable traits.  So genes seem to be underlying a large fraction of the population variation in blood pressure.  Exactly what those genes are or how many genes there are remains to be explored but genes are certainly important. 

《国际循环》： 遗传变异在高血压发展中具有什么作用？
O’Connor教授： 这是一个正在研究中的领域。看上去我们能用的最好证据是家族研究——或家系研究或双生研究或相对危险度研究-同胞研究。我们在人群中可看到的、约一半左右的血压变异属于基因作用的结果。我们称之为“遗传力”。因此，血压一般而言，尤其是高血压，似乎有遗传性状。基因很可能是很多人血压变异的根源。目前还需要探讨有哪些基因或多少基因参与，但是基因肯定很重要。

International circulation:  You say “half”， so what would the other half be?
Prof. Daniel T. O’Connor:  Presumably environment but the unsolved portion of that equation could be environment， either unique environment unique to a given individual or shared environment， environment shared by siblings in a family.  We could also be talking about gene by environment interactions that we have not been able to adequately characterize in families so these are factors where simple heredity would not account for trait variation， probably largely though environment and I think we are all well aware of environmental factors that can influence traits such as blood pressure in particular dietary factors such as sodium consumption.

《国际循环》： 您提到了“一半”，那么剩余一半会怎样？
O’Connor教授：可能与环境有关，尚未明确的部分可能是环境因素——或是针对特定个体的特殊环境，或是共享环境，即家系中的同胞所共享的环境。我们也能通过环境相互作用讨论基因，有时对家系中的特征不能充分说明，单用遗传学不能解释性状的变异，而很可能与环境有关；我想我们都注意到环境因素影响血压这样的特性，尤其是饮食因素，如钠的摄入。

International Circulation:  How close are you in your field to identifying those genes?
Prof. Daniel T. O’Connor:  I think we are very far away.  The current go to technique for identifying such traits is the haplotype map based dense SNP map but this kind of chip is capable of detecting the effects of common alleles or gene variants that affect blood pressure but it is really not capable of detecting rare variants or rare alleles that affect blood pressure so I think we are still very far away from understanding the responsible genetic variants.

《国际循环》： 在您的研究领域中，距离识别这些基因还有多远？
O’Connor教授： 我想我们离得还很远。当前用于识别这样特性的技术是人类基因组单体型图，其根据的是高密度SNP图；但这种类型的芯片适合识别影响血压的普通等位基因或者基因变异的效应，实际上不能识别影响血压的罕见变异或罕见等位基因；因此，我想我们距离理解相关的遗传性变异还很远。

International Circulation:  What is your opinion about hypertension vaccine?
Prof. Daniel T. O’Connor:  You know that is interesting thought.  I think it opens up the general idea of gene therapy or genetic therapy.  Vaccine might be useful in countering the protein which is present in excess in hypertension.  A vaccine would be basically asking your immune system to amount an immune response to such a protein and attack that protein either in the extracellular space or perhaps in the intracellular space depending on where the antibodies could penetrate.  I think virtually nothing has been done in this field so I think this is an area that is a real head scratcher and we do not even have any exploratory data.  One could envision more broadly the possibility of gene therapy approaches were you could either add a component which is depleted in lets say a trait like hypertension， perhaps a vasodilator component.  People are thinking and working on such approaches or you could use reagents such as RNA interference reagents like sRNAs - small interfering RNAs - or hair pin RNAs to try and deplete the expression of a factor which is found to be excessive in hypertension.  Certainly these kinds of things have not been tried at all in humans so it remains a bit speculative but they sure are fun to think about.

《国际循环》： 您如何看待高血压疫苗？
O’Connor教授： 您知道这是一个很有意思的想法。我想这透露出基因治疗或遗传治疗的一般思想。疫苗对抗高血压中出现的过多蛋白时，很有用。一种疫苗首先质问免疫系统，使其产生一种蛋白对抗另一种蛋白的免疫反应，这种反应可以发生在细胞外间隙或细胞内间隙，取决于抗体能否渗入。我想，目前该领域尚未有真正的进展，这是一个很令人头痛的领域，我们甚至没有任何探索性的数据。人们可以大胆设想可能的基因治疗方法，如添加一个组件消除像高血压这样的特性，或添加一个引起血管扩张的组件。大家都在思考和努力实现这种方法，或许可尝试像sRNAs-小的干扰RNAs、或发夹状RNAs这样的RNA干扰试剂，消除某种高血压时过度表达因素的表达。显然这类东西根本不可能在人身上试用，因此还只是一种推测，但的确值得考虑。

International Circulation:  On the subject of prenatal period and hypertension， do you believe it has its origins in the prenatal period?
Prof. Daniel T. O’Connor:  You know there certainly is a lot of evidence consistent with that fact.  For example small for gestational age children tend to be born with kidneys in which nephron numbers are diminished and there are correlations between gestational age and nephron numbers and blood pressure elevation.  So these have been basically replicated at least on a couple of continents that I know about， both in Europe and in the United States and Australia.  I think there is clearly something going on there.  To what extent does variation in birth weight or variation in nephron number account for variation in blood pressure， I think this is an unanswered question.  This is a major player which is dominant in its effect and it is one of many factors which can influence the emergence of blood pressure I still think is an unanswered question.

《国际循环》： 您是否相信妊娠高血压本身起源于产前期？
O’Connor教授： 您知道，对于这个事情实际上已有许多证据支持。例如小于胎龄的儿童出生时容易合并肾脏的肾单位减少，并且孕龄、肾单位数量与血压升高相关。据我所知，至少多个大洲，如欧洲、美国和澳大利亚，基本上都在重复这一现象。我想很明显其中蕴藏着某种关系。尚不清楚出生体重的差异或肾单位数量的差异可在大程度上影响血压的差异。有一种主要因素主导了该效应，但其作为影响血压发生的众多因素之一，对其尚未了解。

International Circulation:  What currently are you working on that would be of interest to our audience? 
Prof. Daniel T. O’Connor:  We have spent a lot of time working on genetic underpinnings of blood pressure.  Using a couple of approaches that we found that are pretty useful， first of all we tend to use large primary care populations and try and pluck out people with the very highest and lowest blood pressure in order to increase our statistic