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Researchers link gene with kidney stones, bone loss in patients who absorb too much calcium

DALLAS April 11, 2002 A team of researchers at UT Southwestern Medical Center has identified a set of genetic abnormalities that increase risk for kidney stones and could indicate increased risk for osteoporosis.

The research teams findings, published in todays edition of the Journal of Clinical Endocrinology and Metabolism, associate six base substitutions deviations from a particular genes normal structure with absorptive hypercalciuria (AH), a condition that makes the intestine absorb too much calcium and causes about 45 percent of all kidney stones.

The presence of at least one of the six base substitutions identified in the study translates into a 2.2- to 3.5-fold increase in the risk of having AH. The presence of more than one of the base substitutions increases risk even more; people who carry any five of the base substitutions are 11.5 times as likely to have AH as those with normal structure in the gene in question, an adenylate cyclase gene.

Dr. Berenice Reed-Gitomer, associate professor of internal medicine and the principal investigator of the study, said there is much to be learned about the molecular mechanism that ties the genetic abnormalities to the resulting disorders, but simply connecting specific genetic abnormalities with AH was an important step. She said it has long been known that kidney-stone formation runs in families, but identifying a genetic connection was elusive.

"We started about 10 years ago looking for a genetic cause," Gitomer said. "We picked out several individual genes that we thought could be involved, but we hit a blank. It would have been like winning the lottery to find it that way."

Gitomer and her team changed their approach. They turned to families with AH and looked for genetic similarities. That comparison pointed to a particular location in the human genome. Through study of the genes from this region, the team focused on a new gene that was similar to a recently described
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Contact: Wayne Carter
Wayne.Carter@UTSouthwestern.edu
214-648-3404
UT Southwestern Medical Center
11-Apr-2002


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