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

This new study, for the first time, extends the findings from patients with rare Mendelian traits to the general population. The findings suggest that independently rare mutations that alter salt handling by the kidneys collectively account for a substantial fraction of the general population's variability in disease susceptibility, said Lifton.

Lifton noted that there are probably about 100 million people worldwide who carry the mutations and are thus protected from hypertension. The mutations we have identified have clinically meaningful effects to individual patients and suggest that independently rare mutations will collectively account for a substantial fraction of the population's variability in disease susceptibility, he said.

The researchers started by examining variations in three genes known to cause rare recessive diseases characterized by large reductions in blood pressure. The analysis was conducted on salt handling genes isolated from people involved in the Framingham Heart Study (FHS), which is directed by Daniel Levy of the National Heart, Lung and Blood Institute. Levy is a co-author of the Nature Genetics report. Co-first authors Weizhen Ji and Jia Ni Foo are at Yale University School of Medicine.

Lifton's team zeroed in on the three salt-regulating genes -- NCCT, NKCC2 and ROMK -- which his group had previously linked to rare but serious human diseases, including Gitelman and Bartter syndromes. Both are conditions characterized by inherited low blood pressure caused by recessive mutations, where two defective copies of a gene are at play.

Salt handing is an essential function of the kidneys. Our kidneys process more than three pounds of salt per day, and genetic mutations that raise or lower the ability of the organ to absorb and process salt can manifest themselves in higher or lower blood pressure.

Lifton's group has searched worldwide for patients with very high or very low blood pressure due to
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
Source:Eurekalert

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