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Association of angiotensinogen haplotypes with angiotensinogen levels but not with blood pressure or coronary artery disease: the Ludwigshafen Risk and Cardiovascular Health Study

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Abstract

Angiotensinogen and its cleaved forms angiotensin I and angiotensin II are important regulators of blood pressure. The gene for angiotensinogen (AGT) carries two common polymorphisms, T207M and M268T (previously described as T174M and M235T). To investigate the role of haplotypes formed by these polymorphisms for angiotensinogen levels we examined blood pressure, coronary artery disease (CAD), myocardial infarction (MI), and AGT genotypes and haplotypes in 2,575 patients with angiographically documented CAD and 731 individuals in whom CAD had been ruled out by angiography. Three haplotypes, designated as Hap1 (T207, M268), Hap2 (T207, T268) and Hap3 (M207, T268), accounted for more than 99% of alleles. The AGT Hap2 haplotype was significantly associated with angiotensinogen levels; one additional Hap2 allele accounted for an approx. 8% increase in angiotensinogen. This association was stronger than that of either single polymorphism. AGT genotypes or haplotypes were not related to hypertension, CAD or MI. We conclude that a common haplotype of the angiotensinogen gene is linked to angiotensinogen levels but has no major impact on blood pressure, hypertension, or cardiovascular risk.

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Abbreviations

ACE :

Angiotensin-converting enzyme

CAD :

Coronary artery disease

LURIC :

Ludwigshafen Risk and Cardiovascular Health

MI :

Myocardial infarction

SNP :

Single-nucleotide polymorphism

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Acknowledgements

We thank Ms. Manuela Gutjahr and Ms. Renate Jahrbacher for their excellent technical assistance. We thank Dr. S. Mathews, Hoffmann LaRoche, Basle, Switzerland, for the recombinant human renin preparation and S. Schilling, Department of Internal Medicine I, University Clinic, Ulm, Germany, for measuring angiotensinogen. We also thank the many members of the LURIC Study team either temporarily or permanently involved in patient recruitment and in sample and data handling and all members of the laboratory teams at Ludwigshafen and Freiburg, Germany.

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Authors and Affiliations

  1. Clinical Institute of Medical and Chemical Laboratory Diagnostics, University and General Hospital, Medical University, Auenbruggerplatz 30, 8036, Graz, Austria

    Wilfried Renner, Hubert Scharnagl & Winfried März

  2. Division of Clinical Chemistry, Department of Medicine, Albert Ludwig University, Freiburg, Germany

    Markus Nauck & Michael M. Hoffmann

  3. Cooperation Unit Pharmacogenomics/Applied Genomics, University of Heidelberg, Heidelberg, Germany

    Bernhard R. Winkelmann

  4. Division of Endocrinology and Diabetes, University of Ulm, Ulm, Germany

    Volker Mayer & Bernhard O. Boehm

Authors
  1. Wilfried Renner
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  2. Markus Nauck
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  3. Bernhard R. Winkelmann
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  4. Michael M. Hoffmann
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  5. Hubert Scharnagl
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  6. Volker Mayer
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  7. Bernhard O. Boehm
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  8. Winfried März
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Correspondence to Wilfried Renner.

Additional information

W. Renner, M. Nauck, and B.R. Winkelmann contributed equally to this manuscript

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Renner, W., Nauck, M., Winkelmann, B.R. et al. Association of angiotensinogen haplotypes with angiotensinogen levels but not with blood pressure or coronary artery disease: the Ludwigshafen Risk and Cardiovascular Health Study. J Mol Med 83, 235–239 (2005). https://doi.org/10.1007/s00109-004-0618-0

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  • DOI: https://doi.org/10.1007/s00109-004-0618-0

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