September 23, 2003

deCODE has identified both at-risk and pretective haplotypes within the PDE4D gene, and is applying its findings to develop novel drugs and diagnostics

deCODE’s landmark study in the genetics of stroke, identifying the first gene ever linked to common forms of the disease, has been published in the online edition of Nature Genetics. The paper, entitled “The Phosphodiesterase 4D gene confers risk to ischemic stroke,” by a deCODE-led team of scientists headed by Solveig Gretarsdottir, is accessible at, and will appear in the October issue of the print edition of the journal.

The deCODE team, working with doctors and researchers at Iceland’s National University Hospital and the Icelandic Heart Association, identified the PDE4D gene and significant haplotypes by analyzing detailed genotypic data from some 1800 participants in its stroke program, both patients and unaffected relatives, from across Iceland.

The study demonstrates that variations in the PDE4D gene are significantly associated with ischemic stroke. Within this gene, the deCODE team identified haplotypes, or specific sets of genetic markers, that correspond both to significantly increased risk of stroke and to significantly decreased risk. Expression and functional analyses of the gene strongly suggest that PDE4D plays an important role in atherosclerosis, most likely by influencing the proliferation and migration of smooth muscle cells within arteries that is central to the biology of ischemic stroke. A drug that could inhibit PDE4D or one of its specific isoforms might therefore be useful in counteracting atherosclerosis, and thereby reducing the risk of stroke. deCODE and its partner in this program, Roche, have initiated medicinal chemistry work on compounds they have identified as active against targets in the PDE4D pathway. deCODE is also developing a DNA-based diagnostic test based upon the at-risk and protective haplotypes within the PDE4D gene.