Impact of Synergistic Polymorphisms in Adrenergic Receptor-Related Genes and Cardiovascular Events in Patients With Dilated Cardiomyopathy

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Author(s)

    • OGIMOTO Akiyoshi
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine
    • OKAYAMA Hideki
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine
    • NAGAI Takayuki
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine
    • SUZUKI Jun
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine
    • INOUE Katsuji
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine
    • NISHIMURA Kazuhisa
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine
    • SHIGEMATSU Yuji
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine
    • TABARA Yasuharu
    • Department of Geriatric Medicine, Ehime University Graduate School of Medicine
    • MIKI Tetsuro
    • Department of Geriatric Medicine, Ehime University Graduate School of Medicine
    • HIGAKI Jitsuo
    • Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine

Abstract

<b><i>Background:</i></b> Sustained cardiac adrenergic stimulation has been implicated in the progression of cardiovascular events in patients with dilated cardiomyopathy (DCM). Our group hypothesized that a combination of polymorphisms that result in increased synaptic norepinephrine release and enhanced receptor function would predispose patients with DCM to cardiovascular events. The effect of polymorphisms in adrenergic receptor-related genes on cardiovascular event-free survival in patients with idiopathic DCM was evaluated. <b><i>Methods and Results:</i></b> Genotyping at 3 loci (<i>ADRB1</i> Ser49Gly and Arg389Gly, and <i>NET</i> T-182C) was performed in 83 patients with DCM. Patients were followed prospectively to the endpoint of cardiovascular events (mean follow-up, 45 months). Cardiovascular events were defined as cardiac death and emergent hospitalization as a result of congestive heart failure, arrhythmia, and cerebrovascular events. Analyses were conducted based on the number of predicted risk genotypes a patient carried. The <i>ADRB1</i> Ser49 allele carrier, <i>ADRB1</i> Arg389 allele carrier, and <i>NET</i>-182CC genotype were defined as the predicted risk genotypes. Cardiovascular event-free survival was compared based on the number of predicted risk genotypes. Cardiovascular event-free survival was significantly better in patients with fewer than 3 predicted risk genotypes than in those with 3 predicted risk genotypes. <b><i>Conclusions:</i></b> Genotyping at these 3 loci might be a useful approach for identification of patients with DCM at risk for cardiovascular events.  (<i>Circ J</i> 2012; <b>76:</b> 2003–2008)<br>

Journal

  • Circulation Journal

    Circulation Journal 76(8), 2003-2008, 2012-07-25

    The Japanese Circulation Society

References:  24

Cited by:  1

Codes

  • NII Article ID (NAID)
    10030505036
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13469843
  • Data Source
    CJP  CJPref  J-STAGE 
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