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'Broken' gene reveals evolution of salt retention and possible ties to hypertension

Researchers at the University of Chicago have found genetic evidence to support the sodium-retention hypothesis, a controversial 30-year-old theory that the high rate of hypertension in certain ethnic groups is caused, in part, by an inherited tendency to retain salt.

In the December issue of the American Journal of Human Genetics, (available now on-line) the researchers show that the frequency of one version of a gene that plays a crucial role in salt retention correlates with distance from the equator. Populations that live in hot, humid climates near the equator tend to have the normal version of that gene, which produces a very effective protein. Populations adapted to cooler climates tend to have a mutant gene that codes for a totally dysfunctional protein.

"The surprise," said study author Anna Di Rienzo, Ph.D., associate professor of human genetics at the University of Chicago, "was finding that as populations moved away from the tropics the original or normal version of the gene became less and less common and the 'broken' version more frequent, which suggests it is protective. There seems to be a strong selective advantage conferred by the non-functioning protein, and that advantage increases with latitude."

"This could change the way we look for disease genes," she added. "Historically, we have searched for mutations, altered or damaged versions of genes that cause rare disorders, like cystic fibrosis or phenylketonuria. Now, we are starting to look for common genes that may have been beneficial in an environment of scarcity, but have become harmful in a world of plenty. In the modern setting, it may often be the genes that aren't damaged that predispose to disease, such as the "thrifty genes" associated with type 2 diabetes."

Humans need salt, sodium chloride, to transport nutrients, transmit nerve impulses or contract muscles, such as the beating heart. The average adult contains about 250 grams of salt, enough to
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Contact: John Easton
John.Easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
28-Oct-2004


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