Basic Research in Cardiology

, Volume 101, Issue 5, pp 447–451

Better identification of patients who benefit from implantable cardioverter defibrillators by genotyping the G protein β3 subunit (GNB3) C825T polymorphism

  • Heinrich Wieneke
  • Christoph N. Naber
  • Leon Piaszek
  • Stefan Sack
  • Ulrich H. Frey
  • Gerd Heusch
  • Raimund Erbel
  • Winfried Siffert



There is a need for better identification of patients at high risk for malignant arrhythmias who would benefit from implantable cardioverter defibrillators (ICD). The purpose of this study was to assess whether the C825T polymorphism in the G-protein beta3 subunit gene, GNB3, might serve as a genetic marker for recurrent ventricular arrhythmias.

Methods and results

Genotyping was performed in 82 patients with ischemic heart disease treated with an ICD for primary and secondary prevention of cardiac arrhythmias. The Kaplan–Meier method was used to estimate the probability of remaining free from VT/VF with cycle length (CL) < 330 ms that required treatment by the ICD. Genotyping yielded 7 individuals homozygous for the 825T allele (TT), 36 homozygous for the C825 allele (CC), and 39 heterozygotes (CT). Multivariate analysis revealed that the C825T polymorphism (P=0.004), left ventricular ejection fraction (P=0.009), and QRS-duration (P=0.039) were independent determinants of severe ventricular arrhythmias. Homozygous carriers of the C825 allele had a 3.9-fold risk for severe ventricular arrhythmias.


The results from this pilot study suggest that the C825T polymorphism may have a modifying effect on the propensity towards life-threatening arrhythmias. Genotyping the C825T polymorphism may help to better identify individuals at high risk for life-threatening arrhythmias who benefit from ICD therapy.


Implantable Cardioverter/Defibrillator G protein beta3 subunit 825T allele GNB3 polymorphism risk stratification ventricular arrhythmia 


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  1. 1.
    Beige J, Hohenbleicher H, Distler A, Sharma AM (1999) G-protein beta3 subunit C825T variant and ambulatory blood pressure in essential hypertension. Hypertension 33:1049–1051PubMedGoogle Scholar
  2. 2.
    Böcker D, Bänsch D, Heinecke A, Weber M, Brunn J, Hammel D, Borggrefe M, Breithardt G, Block M (1998) Potential benefit from implantable cardioverter-defibrillator therapy in patients with and without heart failure. Circulation 98:1636–1643PubMedGoogle Scholar
  3. 3.
    Bode-Schnurbus L, Böcker D, Block, Gradaus R, Heinecke A, Breithardt G, Borggrefe M (2003) QRS duration: a simple marker for predicting cardiac mortality in ICD patients with heart failure. Heart 89:1157–1162PubMedCrossRefGoogle Scholar
  4. 4.
    Buxton AE, Lee KL, DiCarlo L, Gold MR, Greer GS, Prystowsky EN, O’Toole M F, Tang A, Fisher JD, Coromilas J, Talajic M, Hafley G (2000) The Multicenter Unsustained Tachycardia Trial Investigators. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. N Engl J Med 342:1937–1945PubMedCrossRefGoogle Scholar
  5. 5.
    Dobrev D, Wettwer E, Himmel HM, Kortner A, Kuhlisch E, Schuler S, Siffert W, Ravens U (2000) G-Protein beta(3)-subunit 825T allele is associated with enhanced human atrial inward rectifier potassium currents. Circulation 102:692–697PubMedGoogle Scholar
  6. 6.
    Gehi AK, Stein RH, Metz LD, Gomes JA (2005) Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events: a meta-analysis. J Am Coll Cardiol 46:75–82PubMedCrossRefGoogle Scholar
  7. 7.
    Gregoratos G, Abrams J, Epstein AE, Freedman RA, Hayes DL, Hlatky MA, Kerber RE, Naccarelli GV, Schoenfeld MH, Silka MJ, Winters SL, Gibbons RJ, Antman EM, Alpert JS, Gregoratos G, Hiratzka LF, Faxon DP, Jacobs AK, Fuster V, Smith SC Jr (2002) American College of Cardiology/American Heart Association Task Force on Practice Guidelines/North American Society for Pacing and Electrophysiology Committee to Update the 1998 Pacemaker Guidelines. ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation106:2145–2161Google Scholar
  8. 8.
    Huikuri HV, MD, Mäkikallio TH, Raatikainen MJP, Perkiömäki J, Castellanos A, Myerburg RJ (2003) Prediction of sudden cardiac death. Circulation 108: 110–115PubMedCrossRefGoogle Scholar
  9. 9.
    Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML (2002) The multicenter automatic defibrillator implantation trial II investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346:877–883PubMedCrossRefGoogle Scholar
  10. 10.
    Pacifico A, Hohnloser SH, Williams JH, Tao B, Saksena S, Henry PD, Prystowsky EN (1999) Prevention of implantable-defibrillator shocks by treatment with sotalol. N Engl J Med 340:1855–1862PubMedCrossRefGoogle Scholar
  11. 11.
    Pratt CM, Camm J, Bigger JT, Breithardt G, Campbell RWF, Epstein AE, Kappenberger LJ, Kuck KH, Pocock S, Saksena S, Waldo AL (1999) Evaluation of antiarrhythmic drug efficacy in patients with an ICD. Eur Heart J 20:1538–1552PubMedCrossRefGoogle Scholar
  12. 12.
    Rosskopf D, Frey U, Eckhardt S, Schmidt S, Ritz E, Hofmann S, Jaksch M, Muller N, Husing J, Siffert W, Jockel KH (2000) Interaction of the G protein beta 3 subunit T825 allele and the IRS-1 Arg972 variant in type 2 diabetes. Eur J Med Res 30:484–490Google Scholar
  13. 13.
    Ryden M, Faulds G, Hoffstedt J, Wennlund A, Arner P (2002) Effect of the (C825T) Gbeta(3) polymorphism on adrenoceptor-mediated lipolysis in human fat cells. Diabetes 51:1601–1608PubMedGoogle Scholar
  14. 14.
    Schreieck J, Dostal S, von Beckerath N, Wacker A, Flory M, Weyerbrock S, Koch W, Schomig A, Schmitt C (2004). C825T polymorphism of the G-protein beta3 subunit gene and atrial fibrillation: association of the TT genotype with a reduced risk for atrial fibrillation. Am Heart J148:545–550CrossRefGoogle Scholar
  15. 15.
    Seidl K, Hauer B, Schwick NG, Zahn R, Senges J (1998) Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias after the implantation of a cardioverter/defibrillator. Am J Cardiol 82:744–748PubMedCrossRefGoogle Scholar
  16. 16.
    Siffert W, Rosskopf D, Siffert G, Busch S, Moritz A, Erbel R, Sharma AM, Ritz E, Wichmann HE, Jakobs KH, Horsthemke B (2005) Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet 18:45–48CrossRefGoogle Scholar
  17. 17.
    Siffert W (2005) G-protein polymorphisms in hypertension, atherosclerosis, diabetes. Annu Rev Med 56:17–18PubMedCrossRefGoogle Scholar
  18. 18.
    Stein KM, Euler DE, Mehra R, Seidl K, Slotwiner DJ, Mittal S, Markowitz SM, Lerman BB (2002) Do atrial tachyarrhythmias beget ventricular tachyarrythmias in defibrillator recipients. J Am Coll Cardiol 40:335–340PubMedCrossRefGoogle Scholar
  19. 19.
    Verma A, Kilicaslan F, Martin DO, Minor S, Starling R, Marrouche NF, Almahammed S, Wazni OM, Duggal S, Zuzek R, Yamaji H, Cummings J, Chung MK, Tchou PJ, Natale A (2005) Pre-implantation B-type natriuretic peptide level is an independent predictor of future appropriate implantable defibrillator therapies. Heart 92(2):190–195 [Epub ahead of print]PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • Heinrich Wieneke
    • 1
  • Christoph N. Naber
    • 1
  • Leon Piaszek
    • 1
  • Stefan Sack
    • 1
  • Ulrich H. Frey
    • 2
  • Gerd Heusch
    • 3
  • Raimund Erbel
    • 1
  • Winfried Siffert
    • 2
  1. 1.Department of CardiologyUniversity Hospital EssenEssenGermany
  2. 2.Institute of PharmacogeneticsUniversity of Duisburg-EssenGermany
  3. 3.Institute of PathophysiologyUniversity of Duisburg-EssenGermany

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