加州大学圣地亚哥医学分校研究者对超过1200名严重低血压或高血压的患者进行研究后发现一个有趣的结果：基因对血压的影响会因为性别的不同而不同。
“性别象棱镜折射出基因在男性和女性中的不同作用”，加州大学圣地亚哥医学分校医学博士、内科和药理学教授Daniel T. O’Connor这样说。他的研究成果在一月份的《高血压》杂志出版前，已经能够联机使用。
此研究小组发现，性别对基因表达的影响几乎就是一个准则，在南加利福尼亚初级护理病人的大样本研究中，没有一个病人是例外。他们从高加索53，000个病人中，找出血压最高和最低的5%的病人，在平衡了年龄之后，研究剩下的611名男性病人和656名女性病人，发现了性别是如何影响基因表达从而产生如此极端的血压的。
“我们的研究发现一些特定的基因的变异，能够使得一些受体水平上升，而这些受体正是血管紧张素转化酶抑制剂、β受体阻滞剂及其他一些治疗高血压的措施的作用靶点。基因就是通过这种途径从而影响男性和女性的血压。了解这些基因的变异有可能帮助我们更好的诊断、更适当的的治疗高血压”O’Connor说道，“这些发现表明，最适当的治疗很有可能取决于病人的性别。
“高血压是可能引起心力衰竭、中风、肾衰竭的一种严重疾病。一直以来，科学家们都认为高血压是一种遗传因素为主、饮食和一些其他因素协同的家族性疾病。现在我们知道了，在男性和女性中，高血压的发病率以及对治疗的反应也是不同的。举例说：男性比女性的血压要略微高一些。
基于上述差异，研究人员开始验证“基因对血压和高血压的影响是因性别而异”这样一个假设。分子和实验医学系Scripps研究所医学博士Ernst Beutler开展了一个历时两年的血标本收集工作，为了从白细胞中分析DNA。然后研究人员就开始研究收缩压（血压读数中高的数值）和舒张压（血压读数中低的数值）属于非常高或非常低水平的1200位男性和女性病人的基因表型。
此研究在35种编码血压调节作用蛋白的基因中发现了48种基因变异，或叫做多态性。其中，33种基因位于常染色体（两性同源），2种基因位于X染色体（性染色体）。
“35种基因种的6种，在高血压或低血压病人种，在男性和女性之间的变异率时有很大差别的”，O’Connor说。
一些疾病是由于染色体上的单个核苷酸变异引起的，叫做单核苷酸多态性（SNP,读做“snip”）。镰状细胞性贫血和亨庭顿综合症就是这样的疾病，单个变异起了很大的作用。
和这些单个基因性疾病不同，加州大学圣地亚哥医学分校研究者在6个基因中发现了许多细微的改变，表明多个基因参与了高血压的发病过程。“我们发现不止一个基因在高血压的发病中起作用，”O’Connor说：“研究组人员还惊奇的发现这些基因在男性和女性中的影响是不同的“。
这些基因变异中，每个基因变异在男性和女性的血压影响中都是不一样的。48个单核苷酸变异中，两个只在男性中对血压有影响，另两个只在女性中对血压有影响。四个基因变异均表明性别在基因对血压的影响环节中起很大的作用。另有两个基因变异表明，同性中，基因的变异对血压也会产生影响，但无论在男性还是女性中，这种影响和前者相比要小很多。此外，研究者还发现，有几种基因变异，会对男性和女性的血压产生相反的影响。
研究人员总结说：“在根据基因表型制定诊断和治疗高血压的措施的时候，必须把性别的因素考虑进去，才能更精确的辨别基因在疾病的发生、治疗及一系列复杂特征中的作用”。
“什么样的基因变异能更准确的判断病人患高血压的几率，还有待进一步研究，”O’Connor说。
Surprising Interaction Between Genes, Gender, And Hypertension
In surprising results, a study of more than 1,200 patients with extremely low or high blood pressure by researchers at the University of California, San Diego (UCSD) School of Medicine showed that the influence of genes on blood pressure may vary based on gender.
“Sex is like a prism that refracts the effects of the gene very differently for men and women,” said Daniel T. O’Connor, M.D., UCSD professor of Medicine and Pharmacology, whose study is now on-line in advance of publication in the January issue of the journal Hypertension.
The research team found that the gene-by-sex interaction was the rule, not the exception in their study of a large, community-based sample of primary care patients in Southern California. They set out to discover whether gender interacts with genes in contributing to extremes of blood pressure, by looking at the medical records of 611 male and 656 female aged-matched, Caucasian patients whose blood pressure (BP) readings fell in the top and bottom five percent among 53,000 patients.
“Our findings show that specific genetic variations • which give rise to receptors that might be targets for ACE inhibitors or beta-blockers and other therapies used to treat hypertension • impact blood pressure differently in men and women. Knowing these genetic mutations may help us better diagnose hypertension and select the appropriate therapy,” said O’Connor, adding that these findings support that the most appropriate therapy might well depend on whether the patient is a man or a woman.
Hypertension, or high blood pressure, is a serious disease that can result in heart attacks, strokes or kidney failure. Scientists have known for some time that hypertension is a “heritable” condition that runs in families, though diet and other factors also contribute to high blood pressure. It is also known that there are differences in the occurrence of hypertension between men and women, and varied responses to treatments. For example, men normally have slightly higher BP readings than women.
Accounting for these differences, the researchers set out to test their hypothesis that the influence of genes on blood pressure and hypertension varies with a patient’s gender. Ernst Beutler, M.D., of The Scripps Research Institute Department of Molecular and Experimental Medicine, organized a blood sample collection over a two-year period in order to prepare genomic DNA from the patients’ white blood cells. The researchers then focused on the genetic profiles, or genotypes, of more than 1,200 men and women whose systolic (the higher number in a BP reading) and diastolic (lower number) measurements fell at the extreme • highest and lowest • percentiles of distribution.
The study yielded 48 different genetic variations, or polymorphisms, on 35 different genes that encode proteins involved in blood pressure regulation. Thirty-three of the genes were on autosomes (chromosomes found in both sexes), and two were on the “X-linked” or sex chromosomes.
“Of the 35 genes, we found six genes that were quite different in the frequency of variation between people of either sex who had extremely high or low blood pressure,” said O’Connor.
Several diseases are caused by a variation on a single gene on the chromosome, called a single nucleotide polymorphism (SNP, pronounced “snip”). Examples of so-called SNP diseases are sickle-cell anemia and Huntington’s disease, where a single variant or mutation has a dramatic effect.
In contrast to these single-gene-specific diseases, the UCSD researchers observed more subtle variants on six different genes, indicating that multiple genes can contribute to high blood pressure. “We discovered that there’s more than one gene at work in hypertension,” said O’Connor, adding that the team was surprised to find that these SNPs appear to affect men and women differently.
Among the gene variants, each was differently associated with blood pressure measurements in men versus women. Of 48 SNPs, two influenced blood pressure only in men, while two other SNPs contributed only in women. All four SNPs demonstrated significant gender-by-gene interaction effects on blood pressure. Two other SNPs also showed significant gene-by-gender interactions, but their effects were not significant in either men or women alone. Furthermore, the scientists documented several examples where particular gene variations were observed to show directionally opposite effects on blood pressure in men and women.
The researchers conclude that “the results suggest that development of genotype-based diagnostic and therapeutic indices for hypertension must take gender into account to provide an accurate assessment of the role of genes in the origin, treatment and consequences of this complex trait.”
“Further studies may help scientists understand what genetic variables can predict the likelihood of a patient suffering from hypertension,” said O’Connor.
Additional contributors to this paper include Brinda K. Rana, Paul A. Insel, Samuel H. Payne, Kenneth Abel, Michael G. Ziegler and Nicholas J. Schork. Funding for this project was provided by the National Institutes of Health.
http://www.medicalnewstoday.com/medicalnews.php?newsid=59278
编辑：蓝色幻想
