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Gene Associated With Susceptibility To Common Form Of Stroke

 
  September, 23 2003 8:26
your information resource in human molecular genetics
 
     
Scientists at deCODE Genetics in Iceland report in the October issue of Nature Genetics that they have identified a gene that is associated with susceptibility to stroke. Stroke is the third leading cause of death in western countries, and more than 600,000 individuals suffer a stroke each year in the United States.

Solveig Gretarsdottir and colleagues at deCODE had previously mapped a stroke-susceptibility gene to a region on chromosome 5. In the present study, they report a large-scale effort to identify the gene in question involving several hundred people in Iceland who had suffered a stroke. The strongest association was found for the gene PDE4D, linked to susceptibility to ischemic stroke, which is how 80–90% of all strokes are classified. Although there are no variants in the gene itself that are associated with stroke, the authors did show that three different isoforms of the gene were expressed at lower levels in those affected by the disease. Certain combinations of variants in regions flanking the gene were associated with higher or lower risk of stroke.

The gene PDE4D encodes an enzyme called a phosphodiesterase, which breaks down cyclic AMP, a molecule with many biological roles. As defined in animal studies, one such role is in the proliferation and migration of vascular cells, which may be involved in promoting atherosclerosis, a key risk factor for stroke. Gretarsdottir and colleagues suggest that drugs targeting this phosphodiesterase in the at-risk population may prove to be beneficial. Phosphodiesterase inhibitors are already being used to treat asthma, inflammation, and erectile dysfunction (Viagra).

Author contact:

Solveig Gretarsdottir
deCODE Genetics, Reykjavik, Iceland
Tel: +354 5701900
E-mail: solveig.gretarsdottir@decode.is

Also available online.

(C) Nature Genetics press release.


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