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The gene encoding phosphodiesterase 4D confers risk of ischemic stroke

Nature Genetics volume 35, pages 131–138 (2003)Cite this article

A Corrigendum to this article was published on 01 May 2005

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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Figure 1: Expression of PDE4D isoforms in affected individuals and controls.
Figure 2: Single-marker allelic association within PDE4D.
Figure 3: LD and haplotypes at the 5′ end of PDE4D.
Figure 4: Haplotype association for carotid and cardiogenic stroke combined.

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Acknowledgements

We thank the affected individuals and their families whose contribution made this study possible and the nurses at the Icelandic Heart Association, staff at the deCODE core facilities and V. Brophy and S. Cheng for their valuable contribution to this work. Enquiries regarding information and accessibility of the haplotype analysis program NEMO should be addressed to A.K. (augustine.kong@decode.is) or D.G. (daniel.gudbjartsson@decode.is).

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Author notes

  1. Kari Stefansson and Jeffrey R Gulcher: These authors contributed equally to this work.

Authors and Affiliations

  1. deCODE Genetics, Sturlugata 8, Reykjavik, IS-101, Iceland

    Solveig Gretarsdottir, Gudmar Thorleifsson, Sigridur Th Reynisdottir, Andrei Manolescu, Sif Jonsdottir, Thorbjörg Jonsdottir, Thorunn Gudmundsdottir, Sigrun M Bjarnadottir, Olafur B Einarsson, Herdis M Gudjonsdottir, Malcolm Hawkins, Gudmundur Gudmundsson, Hrefna Gudmundsdottir, Hjalti Andrason, Asta S Gudmundsdottir, Matthildur Sigurdardottir, Thomas T Chou, Joseph Nahmias, Shyamali Goss, Mark Gurney, Daniel Gudbjartsson, Michael L Frigge, Augustine Kong, Kari Stefansson & Jeffrey R Gulcher

  2. National University Hospital, Reykjavik, Iceland

    Sigurlaug Sveinbjörnsdottir, Einar M Valdimarsson, Finnbogi Jakobsson & Uggi Agnarsson

  3. Icelandic Heart Association Heart Preventive Clinic, Reykjavik, Iceland

    Vilmundur Gudnason & Gudmundur Thorgeirsson

  4. Pharma Division, Hoffmann-La Roche, Preclinical Research, Basel, Switzerland

    Jurgen Fingerle

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Correspondence to Solveig Gretarsdottir or Jeffrey R Gulcher.

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Competing interests

Some authors (S. Gretarsdottir, G. Thorleifsson, S. T. Reynisdottir, A. Manolescu, S. Jonsdottir, T. Jonsdottir, T. Gudmundsdottir, S. M. Bjarnadottir, O. B. Einarsson, H. M. Gudjonsdottir, M. Hawkins, G. Gudmundsson, H. Gudmundsdottir, H. Andrason, A. S. Gudmundsdottir, M. Sigurdardottir, T. T. Chou, J. Nahmias, S. Goss, M. Gurney, D. Gudbjartsson, M. L. Frigge, A. Kong, K. Stefansson & J. R. Gulcher) are employed by deCODE genetics, and some of them own stock options in the company.

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Gretarsdottir, S., Thorleifsson, G., Reynisdottir, S. et al. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet 35, 131–138 (2003). https://doi.org/10.1038/ng1245

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