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Human Molecular Genetics Advance Access published online on October 4, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi370
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© The Author 2005. Published by Oxford University Press. All rights reserved
Received June 21, 2005
Revised August 11, 2005
Accepted August 26, 2005

Article

The cannabinoid receptor type 2 (CNR2) gene is associated with human osteoporosis

Meliha Karsak 1, Martine Cohen-Solal 2, Jan Freudenberg 3, Agnes Ostertag 2, Caroline Morieux 2, Uwe Kornak 4, Julia Essig 1, Edda Erxlebe 1, Itai Bab 5, Christian Kubisch 6, Marie-Christine de Vernejoul 2, and Andreas Zimmer Ph.D.7*

1 Department of Psychiatry, Life & Brain Center, University of Bonn, 53127 Bonn, Germany
2 INSERM U606 and Department of Rheumatology, Hôpital Lariboisière, 75010 Paris, France
3 Department of Neurology, Laboratories of Neurogenetics, UCSF, San Francisco CA 94143-2922, USA
4 Institute of Medical Genetics, Charité University Hospital, 13353 Berlin, Germany
5 Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
6 Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany
7 Department of Psychiatry, Life & Brain Center, University of Bonn, Sigmund-Freud-strasse 25, 53127 Bonn, Germany

* To whom correspondence should be addressed.
Andreas Zimmer, E-mail: neuro{at}uni-bonn.de


  Abstract

Osteoporosis is one of the most common degenerative diseases. It is characterized by reduced bone mineral density (BMD) with an increased risk for bone fractures. There is a substantial genetic contribution to BMD, although the genetic factors involved in the pathogenesis of human osteoporosis are largely unknown. Mice with a targeted deletion of either the cannabinoid receptor type 1 (Cnr1) or type 2 (Cnr2) genes show an alteration of bone mass and pharmacological modification of both receptors can regulate osteoclast activity and BMD. We therefore analyzed both genes in a systematic genetic association study in a human sample of postmenopausal osteoporosis patients and matched female controls. We found a significant association of single polymorphisms (p-value = 0.0014) and haplotypes (p-value = 0.0001) encompassing the CNR2 gene on human chromosome 1p36, whereas we found no for convincing association for CNR1. These results demonstrate a role for the peripherally expressed CB2-receptor in the etiology of osteoporosis and provide an interesting novel therapeutical target for this severe and common disease.


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