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Impact of β2-adrenoreceptor gene variants on cardiac cavity size and systolic function in idiopathic dilated cardiomyopathy

The Pharmacogenomics Journal volume 7, pages 339–345 (2007)Cite this article

Abstract

In heart failure, the Arg16Gly and Gln27Glu polymorphisms of the β2-adrenoreceptor (β2-AR) gene are associated with exercise-capacity, clinical outcomes and response to β-AR blocker therapy. Whether β2-AR gene variants mediate these effects in-part through an impact on cardiac structural remodeling and pump function independent of the effects of β-blockers is uncertain. We evaluated whether the Arg16Gly and Gln27Glu variants of the β2-AR gene predict left ventricular ejection fraction (LVEF) and LV end diastolic diameter (LVEDD) in patients with idiopathic dilated cardiomyopathy (IDC) before and 6 months after receiving standard medical therapy other than β-AR blockers. In all, 394 patients with IDC and 393 age and gender-matched controls were genotyped for the β2-AR gene variants using restriction-fragment length polymorphism-based techniques. LVEF and dimensions were determined in 132 patients (of whom 71 were newly diagnosed) both at baseline and after 6 months. Genotype of neither variant was associated with the presence of IDC. Moreover, β2-AR genotype did not determine LVEF or LV dimensions prior to initiating therapy. After 6 months of therapy, LVEF increased by 7.1±1.0 absolute units (P<0.0001) and LVEDD decreased by 0.27±0.06 cm (P<0.02). Adjusting for baseline values as well as gender, age, and type of angiotensin-converting enzyme inhibitor therapy received, genotype was associated with neither final LVEF and LVEDD, nor change in LVEF and LVEDD. In conclusion, these data suggest that in heart failure, the functional Arg16Gly and Gln27Glu variants of the β2-AR gene have no independent effect on adverse structural remodeling and pump function.

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Acknowledgements

This research was supported by the University Research Council of the University of the Witwatersrand, the Medical Research Council of South Africa and the HE Griffin Charitable Trust.

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Authors and Affiliations

  1. Cardiovascular Pathophysiology and Genomics Research Unit, Schools of Physiology, University of the Witwatersrand, Johannesburg, South Africa

    D Badenhorst, G R Norton, R Brooksbank, P Sareli & A J Woodiwiss

  2. Medicine (Division of Cardiology, Chris-Hani Baragwanath Hospital), University of the Witwatersrand, Johannesburg, South Africa

    K Sliwa & R Essop

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  1. D Badenhorst
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  2. G R Norton
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  3. K Sliwa
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  4. R Brooksbank
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  7. A J Woodiwiss
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Correspondence to A J Woodiwiss.

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Badenhorst, D., Norton, G., Sliwa, K. et al. Impact of β2-adrenoreceptor gene variants on cardiac cavity size and systolic function in idiopathic dilated cardiomyopathy. Pharmacogenomics J 7, 339–345 (2007). https://doi.org/10.1038/sj.tpj.6500426

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