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Medicineworld.org: Genes have big impact on blood pressure

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Genes have big impact on blood pressure




New Haven, Conn. -Yale University scientists report today in the journal Nature Genetics that they have discovered that rare genetic variants can be linked to a dramatically lower risk of developing hypertension in the general population.

The insight that rare mutations may collectively play a large part in the development of common yet complex diseases such as high blood pressure also has implications for the diagnosis and therapy of diseases such as diabetes and schizophrenia.

The team of scientists was led by Richard Lifton http://www.med.yale.edu/bcmm/RPL/index.html , 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.



Genes have big impact on blood pressure

The researchers 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.

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 scientists speculated that people who carry only one defective copy might be less prone to hypertension.

Lifton's group observed 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 high blood pressure by the time they were 60 than the general population.

A major question in the field of a number of chronic diseases has been whether the risk of developing a disease is more closely associated with common or rare mutations. Recent studies have shown that for a number of 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 linked to the risk of developing hypertension.

So, researchers like Lifton and his lab members Weizhen Ji and Jia Nee Foo have begun to search for the a number of 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 a number of rare variations in genes will collectively account for a large influence on common disease.''.

Lifton said the new study underscores the importance of sequencing the genome of a number of individuals in order to discover disease-causing mutations.

For instance, prior 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 especially promising target for new hypertension treatment.

Eventually, researchers 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.

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".


Posted by: Daniel    Source




Did you know?
New Haven, Conn. -Yale University scientists report today in the journal Nature Genetics that they have discovered that rare genetic variants can be linked to a dramatically lower risk of developing hypertension in the general population. The insight that rare mutations may collectively play a large part in the development of common yet complex diseases such as high blood pressure also has implications for the diagnosis and therapy of diseases such as diabetes and schizophrenia.

Medicineworld.org: Genes have big impact on blood pressure

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