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A locus on chromosome 10 influences C-reactive protein levels in two independent populations

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Abstract

High sensitivity C-reactive protein (hsCRP) is an independent risk factor for cardiovascular disease, such as stroke or coronary artery disease. Genetic factors influence significantly the inter-individual variability of hsCRP. The aim of this study was to identify genomic regions influencing hsCRP levels. A genome scan was performed in two independent studies of Caucasian populations, namely 513 Western-European families ascertained for myocardial infarction (n = 1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In the myocardial infarction families, 31% of the inter-individual variation of hsCRP levels was explained by genetic factors (P = 0.0000015) and loci influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM) with multipoint LOD scores of 3.15 and 2.23, respectively. An additional suggestive signal was detected on chromosome 2 in subset analyses. A similar degree of heritability has been observed in a second independent population of French-Canadian hypertensive families for hsCRP (30%) and linkage results for chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a chromosomal region in two independent populations which influences hsCRP in addition to several unique regions. This provides targets for the identification of genes involved in the regulation of hsCRP and the development and progression of vascular disease, including stroke.

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Acknowledgments

We thank the members of the families for their participation. Moreover, we thank Ms Daniela Hant; B.S., for expert technical assistance and Alexandru Gurau and Pierre-Luc Brunelle for bioinformatics assistance. U.B. and H.J.J. are supported in part by a grants from NHLBI (1P50 HL65203; 1R01 HL 74321). Moreover, we acknowledge the support by the Wilhelm-Vaillant-Stiftung, the Deutsche Herzstiftung, the National Genome Network (NGFN) of the Bundesministerium für Bildung und Forschung, the Cullen Family Run (U.B.), and the Deutsche Forschungsgemeinschaft (C.H., S.H., J.E., and H.S.). The statistical genetic analyses reported here were conducted using the program package SOLAR. SOLAR is supported by U.S. Public Health Service grant MH059490 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Medicine, Medical College of Wisconsin, Milwaukee, USA

    Ulrich Broeckel

  2. Human and Molecular Genetics Center, Medical College of Wisconsin, 8710 Watertown Plank Rd, Milwaukee, WI, 53226, USA

    Ulrich Broeckel, Karen Maresso, Michael Harrison & Howard J. Jacob

  3. Klinik fuer Innere Medizin 2, University of Regensburg, Regensburg, Germany

    Christian Hengstenberg, Stephan Holmer, Christian Glöckner & Guenter A. J. Riegger

  4. Medizinische Klinik 2, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Bjoern Mayer, Jeanette Erdmann & Heribert Schunkert

  5. Université de Montréal, Québec, Canada

    Daniel Gaudet, Johanne Tremblay & Pavel Hamet

  6. Chicoutimi Hospital, Québec, Canada

    Daniel Gaudet

  7. Centre Hospitalier de l’Université de Montréal, Montreal, Canada

    Ondrej Seda, Johanne Tremblay & Pavel Hamet

  8. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati School of Medicine, Cincinnati, USA

    Lisa J. Martin

  9. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, USA

    Jeff T. Williams

  10. Institut fuer Klinische Chemie und Laboratoriumsmedizin, Universitaet Regensburg, Regensburg, Germany

    Gerd Schmitz

  11. Department of Physiology, Medical College of Wisconsin, Milwaukee, USA

    Howard J. Jacob

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  1. Ulrich Broeckel
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  2. Christian Hengstenberg
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  3. Bjoern Mayer
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  4. Karen Maresso
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  8. Stephan Holmer
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  9. Jeanette Erdmann
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  10. Christian Glöckner
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  11. Michael Harrison
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  12. Lisa J. Martin
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  15. Guenter A. J. Riegger
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  16. Howard J. Jacob
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  17. Pavel Hamet
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  18. Heribert Schunkert
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Corresponding authors

Correspondence to Ulrich Broeckel or Heribert Schunkert.

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Ulrich Broeckel and Christian Hengstenberg contributed equally.

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Broeckel, U., Hengstenberg, C., Mayer, B. et al. A locus on chromosome 10 influences C-reactive protein levels in two independent populations. Hum Genet 122, 95–102 (2007). https://doi.org/10.1007/s00439-007-0380-9

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  • DOI: https://doi.org/10.1007/s00439-007-0380-9

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