Human Molecular Genetics Advance Access originally published online on October 4, 2005
Human Molecular Genetics 2005 14(22):3389-3396; doi:10.1093/hmg/ddi370
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Cannabinoid receptor type 2 gene is associated with human osteoporosis
1Department of Psychiatry, Life and Brain Center, University of Bonn, 53127 Bonn, Germany, 2INSERM U606 and Department of Rheumatology, Hôpital Lariboisière, 75010 Paris, France, 3Department of Neurology, Laboratories of Neurogenetics, UCSF, San Francisco, CA 94143-2922, USA, 4Institute of Medical Genetics, Charité University Hospital, 13353 Berlin, Germany, 5Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem 91120, Israel and 6Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany
* To whom correspondence should be addressed at: Department of Psychiatry, Life and Brain Center, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. Tel: +49 2286885300; Fax: +49 2286885301; Email: neuro{at}uni-bonn.de
Received June 21, 2005; Revised August 11, 2005; Accepted August 26, 2005
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) gene 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=0.0014) and haplotypes (P=0.0001) encompassing the CNR2 gene on human chromosome 1p36, whereas we found no 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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