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Genetic variants implicated in telomere length associated with left ventricular function in patients with hypertension and cardiac organ damage

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Abstract

Telomere length has emerged as a biological correlate for ageing, which in turn is a risk factor for the manifestation of cardiovascular diseases. This study investigated the relation between leucocyte telomere length (LTL) and its genetic background to cardiac structure and function in patients with arterial hypertension. We analysed a cohort of 1,106 treated hypertensive patients (83.3% males; mean age, 57.9 ± 9.8 years) with an ejection fraction (EF) over 40% and documented cardiovascular disease or target organ damage. LTL and genotypes of single nucleotide polymorphisms (SNPs), previously implicated in LTL, were determined by real-time PCR. The mean left ventricular mass index (LVMI) and EF were 51.8 ± 21.0 g/H2.7 and 61.1 ± 9.6%, respectively. In multivariate adjusted analysis, a 1.5-fold LTL was positively related with a 2.2% increase of LVMI (CI = 0.1% to 4.2%, p = 0.044) and an absolute increase in EF of 0.6% (CI = 0.1% to 1.1%, p = 0.028). One SNP near TERC (rs16847897) showed a significant absolute difference in EF dependent on allele status (rs16847897, G allele 2.7%; CI = 0.7% to 4.6%; p raw = 0.008, p mt = 0.048, after adjustment for multiple testing). This applied also for two SNPs in BICD1 (rs2630578, C allele −1.8%; CI = −2.8% to −0.7%; p raw = 0.002, p mt = 0.018; rs1151026, G allele −1.9%, CI = −3.0% to −0.8%; p raw < 0.001, p mt = 0.002) with the extension that a frequent haplotype in BICD1 showed an absolute −1.8% (CI = −3.0% to −0.7%; p raw = 0.002, p mt = 0.008) lower EF compared with those lacking this haplotype. Our results point to a role of genetic variants recently implicated in LTL for left ventricular function in hypertensive patients.

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Acknowledgements

We are grateful to all physicians, nurses and patients from the participating centres (listed in the Appendix online). We are particularly grateful to H. Buhlert and K. Stolze who were responsible for central data management and to K. Kossatz for excellent technical assistance. This work was supported by a grant from the Bundesministerium für Bildung und Forschung, Nationales Genomforschungsnetz, Herzkreislaufnetz in NGFNplus (grant number 01GS0839), Germany.

Conflicts of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology and Toxicology, CharitéCentrum für Therapieforschung, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Matthias Huber, Markus Wehland, Ingke Winther, Irina Zergibel, Rona Reibis, Juliane Bolbrinker, Gilbert Schönfelder, Heinz Völler & Reinhold Kreutz

  2. Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Andras Treszl & Karl Wegscheider

  3. Klinik am See, Rehabilitation Center for Cardiovascular Diseases, Rüdersdorf, Germany

    Rona Reibis & Heinz Völler

  4. Leibniz-Institute for Arteriosclerosis Research, University of Münster, Münster, Germany

    Monika Stoll

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  1. Matthias Huber
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  2. Andras Treszl
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  3. Markus Wehland
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Correspondence to Matthias Huber.

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Huber, M., Treszl, A., Wehland, M. et al. Genetic variants implicated in telomere length associated with left ventricular function in patients with hypertension and cardiac organ damage. J Mol Med 90, 1059–1067 (2012). https://doi.org/10.1007/s00109-012-0874-3

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  • DOI: https://doi.org/10.1007/s00109-012-0874-3

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