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Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men

Results of the MONICA Augsburg echocardiographic substudy

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Abstract

Angiotensin-converting enzyme (ACE) activity is considered to be of major importance for the conversion of angiotensin (Ang) I to Ang II. Recently, a second ACE, named ACE2, has been identified. Experimental data provide evidence that ACE2 might be involved in modulating cardiac structure and function. In the present explorative study, we assessed whether polymorphisms in the ACE2 gene are related to echocardiographically determined parameters of left ventricular mass, structure or function in the general population. Five intronic single nucleotide polymorphisms (SNPs) were genotyped using the 5′-exonuclease activity (TaqMan) assay in the echocardiographic substudy of the third MONICA Augsburg survey. As ACE2 is located on the X chromosome, women and men were analysed separately. Four SNPs showed high pairwise linkage disequilibrium (rs4646156, rs879922, rs4240157 and rs233575). The minor alleles of these four SNPs were associated with higher left ventricular mass index (LVMI) and higher septal wall thickness (SWT) in men. Likewise, male carriers of a common haplotype (frequency 29.9%) consisting of the minor alleles of these four SNPs displayed higher values for LVMI and SWT than non-carriers (LVMI: TGGC 98.8±1.52 vs non-TGGC 94.8±0.99 g/m2, p=0.027; SWT: TGGC 11.5±0.14 vs non-TGGC 11.1±0.09 mm, p=0.019). Furthermore, this haplotype was associated with an increased odds ratio (OR) for left ventricular hypertrophy (OR 3.10, p=0.006). In women, similar but less pronounced and consistent trends were observed. No association was observed between any of these SNPs and parameters of left ventricular systolic or diastolic function nor with blood pressure levels. This study provides evidence that genetic variants in the ACE2 gene may be associated with left ventricular mass, SWT and left ventricular hypertrophy in hemizygous men.

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Acknowledgements

This study was supported by the Deutsche Forschungsgemeinschaft (Schu672/9-1, Schu672/10-1, Schu672/12-1, Schu672/14-1, Ho1073/8-1), the Federal Ministry of Research (Dr. Löwel FKZ 01ER9502/0, Dr. Schunkert KBF-FKZ 01GB9403), the National Genome Network (01GS0418 to Dr. Schunkert, Dr. Erdmann and Dr. Hengstenberg and 01GR0466 to Dr. König), The Ernst-and Berta-Grimmke-Stiftung (Dr. Hengstenberg and Dr. Schunkert), the Wilhelm-Vaillant-Stiftung (Dr. Hengstenberg, Dr. Schunkert and Dr. Holmer) and the Deutsche Stiftung für Herzforschung (Dr. Hengstenberg and Dr. Schunkert).

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Authors and Affiliations

  1. Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Wolfgang Lieb, Anika Götz, Björn Mayer, Jan Stritzke, Heribert Schunkert & Jeanette Erdmann

  2. Institut für Humangenetik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

    Wolfgang Lieb

  3. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

    Jochen Graf, Marcus Fischer, Christian Hengstenberg & Stephan R. Holmer

  4. Institut für Medizinische Biometrie und Statistik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

    Anika Götz & Inke R. König

  5. Institut für Epidemiologie, GSF Nationales Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany

    Angela Döring & Hannelore Löwel

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  1. Wolfgang Lieb
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  9. Stephan R. Holmer
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Corresponding author

Correspondence to Jeanette Erdmann.

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W. Lieb and J. Graf contributed equally to this work

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Lieb, W., Graf, J., Götz, A. et al. Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. J Mol Med 84, 88–96 (2006). https://doi.org/10.1007/s00109-005-0718-5

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  • DOI: https://doi.org/10.1007/s00109-005-0718-5

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