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The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample

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Abstract

Genetic variants within the CNR2 gene encoding the cannabinoid receptor CB2 have been shown to be associated with osteoporosis and low bone mineral density (BMD) in case-control studies. We now examined the association of polymorphisms in CNR2 with hand bone strength in an ethnically homogeneous healthy family sample of European origin (Chuvashians) living in Russia. We show that non-synonymous CNR2 SNPs are significantly associated with radiographic hand BMD and breaking bending resistance index (BBRI) by two different transmission disequilibrium tests. For both tests highly significant p values (ranging from 0.007 to 0.008 for hand BMD, and from 0.001 to 0.003 for BBRI) were also obtained with additional SNPs at the CNR2 locus. The associations remained significant after correction for multiple testing. In conclusion, in addition to the association of CNR2 polymorphisms with low BMD at selected clinically relevant skeletal sites, we now report their significant association with hand bone strength phenotypes using a family-based study design implying an even broader impact of genetic variation at the CNR2 locus on bone structure and function.

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Acknowledgments

We thank the patients for their cooperation and Julia Essig and Edda Erxlebe for excellent technical assistance. This work was supported by DFG grant (FOR 926 and SFB 645 to MK and AZ) and by Recanati foundation grant to GL.

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Authors and Affiliations

  1. Department of Molecular Psychiatry, Life and Brain Center, University of Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany

    Meliha Karsak & Andreas Zimmer

  2. Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel

    Ida Malkin & Gregory Livshits

  3. Institute for Genetics, University of Cologne, Cologne, Germany

    Mohammad R. Toliat, Christian Kubisch & Peter Nürnberg

  4. Cologne Center for Genomics, University of Cologne, Cologne, Germany

    Mohammad R. Toliat & Peter Nürnberg

  5. Institute of Human Genetics, University of Cologne, Cologne, Germany

    Christian Kubisch

  6. Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany

    Christian Kubisch

  7. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

    Christian Kubisch & Peter Nürnberg

  8. Yoran Institute for Human Genome Research, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Gregory Livshits

Authors
  1. Meliha Karsak
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  2. Ida Malkin
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  3. Mohammad R. Toliat
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  4. Christian Kubisch
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  6. Andreas Zimmer
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Correspondence to Meliha Karsak or Gregory Livshits.

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Karsak, M., Malkin, I., Toliat, M.R. et al. The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample. Hum Genet 126, 629–636 (2009). https://doi.org/10.1007/s00439-009-0708-8

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  • DOI: https://doi.org/10.1007/s00439-009-0708-8

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