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Association between endothelin type A receptor haplotypes and mortality in coronary heart disease

    Katrina L Ellis

    * Author for correspondence

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand.

    ,
    Anna P Pilbrow

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    ,
    Howard C Potter

    Molecular Pathology Laboratory, Canterbury District Health Board, Christchurch, New Zealand

    ,
    Chris M Frampton

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    ,
    Rob N Doughty

    Department of Medicine, Faculty of Medicine & Health Sciences, University of Auckland, Auckland, New Zealand

    ,
    Gillian A Whalley

    Department of Medicine, Faculty of Medicine & Health Sciences, University of Auckland, Auckland, New Zealand

    Department of Medical Imaging, Unitec Institute of Technology, Auckland, New Zealand

    ,
    Chris J Ellis

    Department of Medical Imaging, Unitec Institute of Technology, Auckland, New Zealand

    ,
    Barry R Palmer

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    ,
    Lorraine Skelton

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    ,
    Tim G Yandle

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    ,
    Richard W Troughton

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    ,
    A Mark Richards

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    &
    Vicky A Cameron

    Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand

    Published Online:https://doi.org/10.2217/pme.12.10

    Aims: The endothelin type A receptor, encoded by EDNRA, mediates the effects of endothelin-1 to promote vasoconstriction, vascular cell growth, adhesion, fibrosis and thrombosis. We investigated the association between EDNRA haplotype and cardiovascular outcomes in patients with coronary artery disease. Methods: Coronary disease patients (n = 1007) were genotyped for the His323His (rs5333) variant and one tag SNP from each of the major EDNRA haplotype blocks (rs6537484, rs1568136, rs5335 and rs10003447). EDNRA haplotype associations with clinical history, natriuretic peptides cardiac function and cardiovascular outcomes were tested over a median 3.8 years. Results: Univariate analysis identified a ‘low-risk’ EDNRA haplotype associated with later age of Type 2 diabetes onset (p = 0.004) smaller BMI (p = 0.021), and reduced mortality (log rank p = 0.001). Cox proportional hazards analysis including established cardiovascular risk factors revealed an independent association between haplotype and mortality (p < 0.0001). Conclusion: These data highlight the potential importance of the endothelin system, and in particular EDNRA in coronary disease.

    Papers of special note have been highlighted as: ▪ of interest

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