JACC
HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
QUICK SEARCH:   [advanced]


     

J Am Coll Cardiol, 2003; 41:190-194
© 2003 by the American College of Cardiology Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Snapir, A.
Right arrow Articles by Karhunen, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Snapir, A.
Right arrow Articles by Karhunen, P. J.

CLINICAL STUDY: CARDIAC ARREST AND PULMONARY EDEMA

Variation in the alpha2B-adrenoceptorgene as a risk factor for prehospitalfatal myocardial infarction and sudden cardiac death

Amir Snapir, MD*,*, Jussi Mikkelsson, MD, PhD{dagger}, Markus Perola, MD, PhD{ddagger}, Antti Penttilä, MD, PhD§, Mika Scheinin, MD, PhD* and Pekka J. Karhunen, MD, PhD{dagger}

* Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland
{dagger} Medical School, University of Tampere and Tampere University Hospital, Tampere, Finland
{ddagger} UCLA Department of Human Genetics, Gonda Neuroscience and Genetics Research Center, Los Angeles, California, USA
§ Department of Forensic Medicine, University of Helsinki, Helsinki, Finland

Manuscript received June 5, 2002; revised manuscript received September 23, 2002, accepted October 4, 2002.

* Reprint requests and correspondence: Dr. Amir Snapir, Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4, FIN-20520 Turku, Finland.
snapir{at}utu.fi

OBJECTIVES: Our aim was to corroborate the observed association between the deletion/deletion (DD) genotype of the insertion/deletion polymorphism in the alpha2B-adrenoceptor (AR) and increased risk for acute myocardial infarction (AMI), and to study whether this genotype also confers an increased risk for sudden cardiac death (SCD).

BACKGROUND: Vasospasm has been suggested to play a role in AMI. Alpha2-AR mediate coronary vasoconstriction in humans, and studies on mice suggest the involvement of the alpha2-AR subtype B in vasoconstriction. A deletion variant of the human alpha2B-AR has been associated with impaired receptor desensitization in vitro. In a population-based prospective study of 912 middle-aged men, the DD genotype of the alpha2B-AR conferred an increased risk for AMI.

METHODS: A series of 700 unselected sudden out-of-hospital deaths of middle-aged white men subjected to medico-legal autopsy was analyzed.

RESULTS: Genotype information was obtained for 683 men (DD = 22%, insertion/deletion = 51%, insertion/insertion = 27%). Carriers of the DD genotype had an increased risk for SCD (n = 278, odds ratio [OR] = 2.0, p = 0.01) and fatal AMI (n = 84, OR = 2.1, p = 0.04) compared with the other two genotypes combined. The risks for SCD and fatal AMI were higher in carriers of the DD genotype who died before the age of 55 years (OR = 4.5 and 5.0, p < 0.001 for both).

CONCLUSIONS: Middle-aged white men carrying the DD genotype of the alpha2B-AR have a significantly increased risk for SCD and AMI, especially before the age of 55 years.

Abbreviations and Acronyms
  AMI
  acute myocardial infarction
  AR
  adrenoceptor
  CHD
  coronary heart disease
  CI
  confidence interval
  DD
  deletion/deletion
  DNA
  deoxyribonucleic acid
  HSDS
  Helsinki Sudden Death Study
  ID
  insertion/deletion
  II
  insertion/insertion
  MI
  myocardial infarction
  OR
  odds ratio
  SCD
  sudden cardiac death




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
T. C. Sichrovsky, S. Mittal, and J. S. Steinberg
Dexmedetomidine Sedation Leading to Refractory Cardiogenic Shock
Anesth. Analg., June 1, 2008; 106(6): 1784 - 1786.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. C. Duling, T. W. Cherng, J. R. Griego, M. F. Perrine, and N. L. Kanagy
Loss of {alpha}2B-adrenoceptors increases magnitude of hypertension following nitric oxide synthase inhibition
Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2403 - H2408.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al.
ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)
J. Am. Coll. Cardiol., September 5, 2006; 48(5): e247 - e346.
[Full Text] [PDF]

Home page
 EuropaceHome page
Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al.
ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Europace, September 1, 2006; 8(9): 746 - 837.
[Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S. Kaab and E. Schulze-Bahr
Susceptibility genes and modifiers for cardiac arrhythmias
Cardiovasc Res, August 15, 2005; 67(3): 397 - 413.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
J. P. Etzel, B. K. Rana, G. Wen, R. J. Parmer, N. J. Schork, D. T. O'Connor, and P. A. Insel
Genetic Variation at the Human {alpha}2B-Adrenergic Receptor Locus: Role in Blood Pressure Variation and Yohimbine Response
Hypertension, June 1, 2005; 45(6): 1207 - 1213.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. N. Desai, K. M. Standifer, and D. C. Eikenburg
Simultaneous {alpha}2B- and {beta}2-Adrenoceptor Activation Sensitizes the {alpha}2B-Adrenoceptor for Agonist-Induced Down-Regulation
J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 794 - 802.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
D. E. Arking, S. S. Chugh, A. Chakravarti, and P. M. Spooner
Genomics in Sudden Cardiac Death
Circ. Res., April 2, 2004; 94(6): 712 - 723.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
S. L. Kirstein and P. A. Insel
Autonomic Nervous System Pharmacogenomics: A Progress Report
Pharmacol. Rev., March 1, 2004; 56(1): 31 - 52.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
J. O. Ruuskanen, H. Xhaard, A. Marjamaki, E. Salaneck, T. Salminen, Y.-L. Yan, J. H. Postlethwait, M. S. Johnson, D. Larhammar, and M. Scheinin
Identification of Duplicated Fourth {alpha}2-Adrenergic Receptor Subtype by Cloning and Mapping of Five Receptor Genes in Zebrafish
Mol. Biol. Evol., January 1, 2004; 21(1): 14 - 28.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
G. Heusch
Emerging importance of alpha-adrenergic coronary vasoconstriction in acute coronary syndromes and its genetic background
J. Am. Coll. Cardiol., January 15, 2003; 41(2): 195 - 196.
[Full Text] [PDF]


HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
Copyright © 2003 by the American College of Cardiology Foundation.