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The variable number of tandem repeat polymorphism in the P-selectin glycoprotein ligand-1 gene is not associated with coronary heart disease

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Abstract

Genes involved in inflammatory processes are candidates for predisposition to prothrombotic syndromes. The variable number of tandem repeat (VNTR) polymorphism in the P-selectin glycoprotein ligand (PSGL)-1 gene has been associated with ischemic cerebrovascular disease but not with coronary heart disease (CHD). We assessed the effect of the VNTR polymorphism on CHD in two independent case/control studies. In the first study 281 CHD patients and 397 healthy blood donors were genotyped for the VNTR alleles in PSGL-1. The prevalence of homozygous carriers of the PSGL-1 VNTR allele with 15 repeat units was significantly higher in the CHD patients (5.3% vs. 1.5%) than in controls, suggesting an effect of this marker in CHD. To validate the findings genotyping was performed in a second study including 2,578 CHD patients, 731 patients without CHD, and 1084 healthy blood donors. The larger case control study had a power of 99.9% to detect the initially observed difference but failed to confirm the putative role of PSGL-1 VNTR polymorphism in CHD. Frequencies of the PSGL-1 VNTR 15 repeats for homozygous carriers were 2.2% in healthy blood donors, 2.3% in patients without CHD and 2.7%, in CHD cases, respectively. These results demonstrate that the PSGL-1 VNTR polymorphism is not a genetic risk factor for CHD. Adequately powered studies are prerequisites to obtain reliable results about genotype-phenotype relationships of new candidate genes in complex diseases.

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Abbreviations

CHD :

Coronary heart disease

CVD :

Cerebrovascular disease

LURIC :

Ludwigshafen Risk and Cardiovascular Health

PSGL :

P-selectin glycoprotein ligand

VNTR :

Variable number of tandem repeat

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Acknowledgements

This work was supported by the research program MIGROVAS of the Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany. We wish to thank Sonja Mattler for expert technical assistance. We also thank the many members of the LURIC study team either temporarily or permanently involved in patient recruitment, sample, and data handling, and all members of the laboratory team involved with genotyping the LURIC samples at the University Hospital Freiburg, Germany.

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Authors and Affiliations

  1. Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg–Hessia, Ruprecht Karl University Heidelberg, Faculty of Clinical Medicine Mannheim, Friedrich-Ebert-Strasse 107, 68167, Mannheim, Germany

    Peter Bugert, Marion Vosberg & Harald Klüter

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

    Michael M. Hoffmann & Winfried März

  3. Cooperation Unit Pharmacogenomics/Applied Genome Research, Department of Internal Medicine VI (Clinical Pharmacology and Pharmacoepidemiology) and Coordination Center for Clinical Trials, Ruprecht Karl University, Heidelberg, Germany

    Bernhard R. Winkelmann

  4. Medical Clinic II, Medical School, University of Lübeck, Lübeck, Germany

    Jürgen Jahn & Matthias Entelmann

  5. Department of Internal Medicine III, University Hospital, Heidelberg, Germany

    Hugo A. Katus

  6. Institute of Medical Biometry and Informatics, Ruprecht Karl University, Heidelberg, Germany

    Ulrich Mansmann

  7. Division of Endocrinology, Department of Internal Medicine I, University Hospital, Ulm, Germany

    Bernhard O. Boehm

  8. Institute of Immunology and Transfusion Medicine, Medical School, University of Lübeck, Lübeck, Germany

    Siegfried Goerg

Authors
  1. Peter Bugert
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  2. Michael M. Hoffmann
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  3. Bernhard R. Winkelmann
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  4. Marion Vosberg
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  5. Jürgen Jahn
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  6. Matthias Entelmann
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  7. Hugo A. Katus
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  8. Winfried März
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  9. Ulrich Mansmann
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  10. Bernhard O. Boehm
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  11. Siegfried Goerg
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  12. Harald Klüter
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Corresponding author

Correspondence to Peter Bugert.

Additional information

P. Bugert, M.M. Hoffmann, and B.R. Winkelmann, contributed equally to this work

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Bugert, P., Hoffmann, M.M., Winkelmann, B.R. et al. The variable number of tandem repeat polymorphism in the P-selectin glycoprotein ligand-1 gene is not associated with coronary heart disease. J Mol Med 81, 495–501 (2003). https://doi.org/10.1007/s00109-003-0459-2

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  • DOI: https://doi.org/10.1007/s00109-003-0459-2

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