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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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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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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DOI: https://doi.org/10.1038/ng1245
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