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Mayo: Variants in gene on X chromosome associated with increased susceptibility to Alzheimer's
Date:1/11/2009

JACKSONVILLE, Fla. Researchers at Mayo Clinic have discovered the first gender-linked susceptibility gene for late-onset Alzheimer's disease.

In the Jan. 11 online edition of Nature Genetics, they report the results of their two-stage genome-wide association study of patients with Alzheimer's disease. The research showed that women who inherited two copies of a variant in the PCDH11X gene, found on the X chromosome, are at considerably greater risk of developing Alzheimer's disease. Women with a variant on one of their two X chromosomes also had some increase in risk, as did men with the variant on their single X chromosome, but these effects were weaker than inheriting two variants.

Investigators caution that more study is required before assigning the definitive degree of risk the gene seems to carry, but they say it appears to be one of the stronger risk factors found to date.

"This is a very common genetic variant, and many women who had two copies of it did not have disease. But, overall, the odds were substantially greater that female patients with the disease did have two copies," says the study's senior investigator, Steven Younkin, M.D., Ph.D., a consultant-researcher at Mayo Clinic's campus in Florida and George M. Eisenberg, Professor of Neuroscience in the College of Medicine. "The results obtained do not imply that women are generally at increased risk for developing the disease than men."

The Mayo group first detected a variant in the gene PCDH11X, which associates with susceptibility to Alzheimer's disease, by scanning the entire genome of 844 patients affected with Alzheimer's disease and 1,255 unaffected control subjects. The association was confirmed by studying an additional 1,547 patients and 1,209 controls.

The variant was found in 79 percent of unaffected women; 50 percent had one copy and 29 percent had two. Since men have one X and one Y chromosome and women have two X chromosomes,
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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

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