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The gene encoding phosphodiesterase 4D confers risk of ischemic stroke |
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| Authors: | Gretarsdottir Solveig Thorleifsson Gudmar Reynisdottir Sigridur Th Manolescu Andrei Jonsdottir Sif Jonsdottir Thorbjörg Gudmundsdottir Thorunn Bjarnadottir Sigrun M Einarsson Olafur B Gudjonsdottir Herdis M Hawkins Malcolm Gudmundsson Gudmundur Gudmundsdottir Hrefna Andrason Hjalti Gudmundsdottir Asta S Sigurdardottir Matthildur Chou Thomas T Nahmias Joseph Goss Shyamali Sveinbjörnsdottir Sigurlaug Valdimarsson Einar M Jakobsson Finnbogi Agnarsson Uggi Gudnason Vilmundur Thorgeirsson Gudmundur Fingerle Jurgen Gurney Mark Gudbjartsson Daniel Frigge Michael L Kong Augustine Stefansson Kari |
| Affiliation: | deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland. solveig.gretarsdottir@decode.is |
| Abstract: | We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke. |
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