Researchers discover new route to high blood pressure

After years of detailed genetic analysis, researchers have discovered two genes that underlie a new metabolic pathway that governs blood pressure in humans. These findings could offer novel molecular targets for new blood pressure medicines.

High blood pressure affects about one-quarter of all adults worldwide and is an important risk factor for death from stroke, heart disease and congestive heart and kidney failure. In an article published in the August 10, 2001, issue of the journal Science, an international research team led by Howard Hughes Medical Institute investigator Richard P. Lifton at Yale University School of Medicine reported identifying two genes that cause pseudohypoaldosteronism type II (PHAII). This disorder leads to hypertension by causing increased reabsorption of salt by the kidneys and impaired secretion of potassium and hydrogen ions.

Although the disorder seemed to point to a previously unknown cause of hypertension, said Lifton, tracing its genetic roots in affected families proved difficult. "In contrast to the other single-gene forms of high blood pressure we have studied, PHAII was complicated," he said. "Patients with the disorder get hypertension as adults -- rather than as children -- like the majority of people with hypertension, and the abnormal potassium and acidity levels are variable. This complicated unraveling the genetics."

After attempting to trace the genetics of the disease in numerous affected families, Lifton and his colleagues identified two types of families -- one with a gene mutation on chromosome 12, and the other with a mutation on chromosome 17. This provided researchers with the information they needed to begin to zero in on the genomic location of the mutated genes.

In analyzing genetic data from a family with a mutation on chromosome 12, the researchers determined that the disorder appeared to be due to a deletion of a segment of DNA in a large region of the chromosome. Fortunatel

Contact: Jim Keeley
Howard Hughes Medical Institute

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