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Yale Study Shows How Rare Genes Have Big Impact On Blood Pressure
Article Date: 06 Apr 2008 - 13:00 PDT
Yale University researchers report in the journal Nature Genetics that they have discovered that rare genetic variants can be associated with a dramatically lower risk of developing high blood pressure in the general population.
耶鲁大学研究人员在自然遗传学杂志中报道他们已经发现了普通人群中罕见基因变异与高血压发展低风险性的关联。
The insight that rare mutations may collectively play a large part in the development of common yet complex diseases such as hypertension also has implications for the diagnosis and treatment of diseases such as diabetes and schizophrenia.
关于罕见突变可能在复杂性疾病如高血压的发生发展中共同发挥作用的启示也为诸如糖尿病和精神分裂症的诊断与治疗提供线索。
The team of researchers was led by Richard Lifton, chair of the Department of Genetics and Sterling Professor of Genetics and Internal Medicine at Yale, and Daniel Levy, director National Heart, Lung and Blood Institute's Framingham Heart Study.
这项研究是由耶鲁大学遗传学和内科学教授、遗传学系主席Richard Lifton和国立心脏、肺和血液研究院的Framingham心脏研究主任Daniel Levy主持的。
The scientists analyzed DNA samples from 3,125 people who participated in the Framingham Heart Study, a long-running epidemiology survey that has led to a treasure trove of information about the causes of heart disease.
科学家们分析了参与Framingham 心脏研究（一项长期的关于心脏病发病原因的流行病学调查）3125人的DNA样本。
They decided to study the health impact of three genes regulating the processing of salt in the kidney and each known to cause dangerously low blood pressure levels when inherited with two defective copies (one from each parent). The researchers speculated that people who carry only one defective copy might be less prone to hypertension.
他们决定研究调节肾脏中盐代谢过程的三个基因对健康的影响以及当遗传两个（父母双方各一个）缺陷基因时可以引起危险性低血压水平的每个已知基因对健康的影响。研究人员推测只携带一个缺陷基因的人可能更容易发生高血压。
Lifton's group found that 2 percent of the subjects carried one defective copy of one of the three genes. These individuals in general had lower blood pressure and a 60 percent lower risk of developing hypertension by the time they were 60 than the general population.
Lifton小组发现2%的受试者携带三个基因中的一个缺陷基因。这些人一般都有低血压，而到他们60岁的时候发展为高血压的风险比普通人低60%。
A major question in the field of many chronic diseases has been whether the risk of developing a disease is more closely linked to common or rare mutations. Recent studies have shown that for many diseases, common genetic variants can only explain a small fraction of an individual's risk of developing the condition. In the case of high blood pressure, for instance, large genome-wide studies have thus far found no common variants that are associated with the risk of developing hypertension.
许多慢性病的主要问题在于发病风险与普通突变密切相关还是与罕见突变密切相关。最近的研究表明对于许多疾病来说，普通的基因变异仅仅能解释一小部分个体发病的风险。而对于高血压来说，大型基因组范围研究还未发现与高血压发病风险相关联的普通变异。
So, scientists like Lifton and his lab members Weizhen Ji and Jia Nee Foo have begun to search for the many rare mutations that might have a larger impact on the risk of inherited diseases on smaller groups of people. \"Collectively, common variants have explained a small fraction of the risk of most diseases in the population, as we would expect from the effects of natural selection,'' Lifton explained. \"The question this leaves open is whether many rare variations in genes will collectively account for a large influence on common disease.''
所以，科学家们如Lifton和其实验室同事Weizhen Ji 、Jia Nee Foo开始寻找一些可能对少数人患遗传性疾病影响更大的罕见基因突变。Lifton解释道：“像我们从自然选择的效应中所期待的那样，普通变异已经解释人群中大多数疾病风险的一小部分。问题在于基因中许多罕见突变是否能够共同解释对疾病的巨大影响。”
Lifton said the new study underscores the importance of sequencing the genome of many individuals in order to discover disease-causing mutations.
Lifton说新的研究强调了为了发现引起疾病的突变而测定人类基因组的重要性。
For instance, previous genetic studies of hundreds of families with severely low blood pressure enabled his team to identify the gene mutations used in the study. And one of the genes, ROMK, has turned out to be a particularly promising target for new high blood pressure therapy.
例如，以前的数百个患有严重低血压的家族基因研究使其小组识别了研究中所用的基因突变。其中一个基因ROMK成为新型高血压治疗的一个特别有前途的靶基因。
Eventually, scientists may find dozens of genes in which rare mutations individually account for a low percentage of common diseases among individuals, but may collectively account for the burden of common chronic diseases, Lifton said.
Lifton说最后科学家们可能会找到数个基因，这些基因单个的罕见突变可以解释个体中普通疾病的低发病率，但也可能共同解释普通慢性病的负担
Added Levy, \"We may have to march down the field from gene to gene to identify other genes where rare variants are contributing to blood pressure variations.\"
Levy补充道：“我们要从一个基因到一个基因进行下去来识别其他可能因为基因罕见突变而导致血压变异的基因。”
Nature Genetics, Advanced Online Edition, April 6.
自然遗传学进展在线版（4.6） |
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发表于 2008-4-21 11:47:49