Cannabinoid receptor type 2 gene is associated with human osteoporosis.
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.
Karsak
Meliha
M
Department of Psychiatry, Life and Brain Center, University of Bonn, Germany.
Cohen-Solal
Martine
M
Freudenberg
Jan
J
Ostertag
Agnes
A
Morieux
Caroline
C
Kornak
Uwe
U
Essig
Julia
J
Erxlebe
Edda
E
Bab
Itai
I
Kubisch
Christian
C
de Vernejoul
Marie-Christine
MC
Zimmer
Andreas
A
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*
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2