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

the variant occurred in only 46 percent of unaffected men where a single copy was present. "When we compared Alzheimer's disease patients with unaffected controls, the largest and most significant difference was in women with two copies of the PCDH11X variant, who were found more frequently in the Alzheimer's disease group," Dr. Younkin says. "Compared to female non-carriers, the odds ratio was 1.75 for women with two copies of the variant and 1.26 for women with one copy. It was 1.18 for men with one copy compared to male non-carriers."

To put these findings in context, the odds ratio for two copies of the well-established, high-risk APOE 4 allele was 11.5 in the subjects assembled by the Mayo group, and it was 4.8 for one copy, Dr. Younkin says. APOE 4 is the highest-risk Alzheimer's disease susceptibility allele found to date. The association for women with one copy of the PCDH11X variant is similar to genetic associations now being reported for many diseases, but the strength of association when two copies were present is noteworthy particularly because the PCDH11X variant is so common, investigators say.

"It is always exciting to identify a new Alzheimer's disease gene," says Minerva Carrasquillo, Ph.D., instructor of neuroscience and first author of the study. "The search for genes that influence the risk of common complex diseases such as Alzheimer's disease has proven extremely difficult, as most of the genes involved in the etiology of such diseases tend individually to have only modest effects on risk.

"When we set out to scan the genome for Alzheimer's disease susceptibility genes, we were not at all certain that we would find any gene other than the well-established APOE gene. Fortunately, the unbiased genome-wide scan that we undertook enabled us to identify PCDH11X, a previously unsuspected gene on the X chromosome that is the first to show gender-specific effects."

Dr. Younkin says, "Even though this is a large stud
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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

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