title: Cannabinoid receptor type 2 gene is associated with human osteoporosis.
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) 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.
authors.affiliation: Department of Psychiatry, Life and Brain Center, University of Bonn, Germany.
authors.forename: Meliha
authors.initials: M
authors.lastname: Karsak
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Solal
authors.forename: Jan
authors.initials: J
authors.lastname: Freudenberg
authors.forename: Agnes
authors.initials: A
authors.lastname: Ostertag
authors.forename: Caroline
authors.initials: C
authors.lastname: Morieux
authors.forename: Uwe
authors.initials: U
authors.lastname: Kornak
authors.forename: Julia
authors.initials: J
authors.lastname: Essig
authors.forename: Edda
authors.initials: E
authors.lastname: Erxlebe
authors.forename: Itai
authors.initials: I
authors.lastname: Bab
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: de Vernejoul
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D005260:Female; D006801:Humans; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*
chemical_list: D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2