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Rare genetic mutations protect against hypertension
Date:4/6/2008

mutations in single genes. Such patients are often identified through family histories of extreme blood pressure. To date, his group has found a score of gene mutations that lower or raise blood pressure, including those that cause the extreme low blood pressure found in patients with Gitelman and Bartter syndromes.

We used knowledge of the spectrum of mutations that cause Gitelman and Bartter syndromes to sort among the hundreds of sequence changes we observed to identify those that are either known or highly likely to alter the function of the (gene) encoded proteins, Lifton explained.

By sequencing each of the three genes obtained from DNA samples from 3,125 participants in the Framingham Heart Study, and doing additional biochemical, genetic and genomic analysis, the HHMI team found functional mutations in one of the genes in at least 1 of every 64 of the study's participants sampled.

The results show that nearly 2 percent of the FHS cohort has a defective copy of one of these three genes, Lifton said. Unlike patients with Gitelman and Bartter syndromes, these subjects have only one defective copy, not two.

Lifton's group then tracked the influence of the mutation on blood pressure in FHS subjects aged 40-60, a time of life when hypertension manifests itself and can pose serious health risks.

We found that these mutation carriers have a 60 percent reduction in their risk of developing hypertension and have significantly lower blood pressure than those who do not have mutations, Lifton said. The influence of the mutation, he added, approximates effects achieved with drugs used to lower blood pressure.

The practical upshot of the new work, according to Lifton, could be potential new drugs to mimic the effects of the mutation by selectively inhibiting a single gene or several genes.

In addition, the study more broadly underscores the value of genetic analysis -- resequencing of genes and genomes to ferret
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
Source:Eurekalert

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