Cannabinoid receptor gene polymorphisms and bone mineral density in Korean postmenopausal women.

OBJECTIVE: We investigated the association between single nucleotide polymorphisms in cannabinoid receptor (CNR) genes and bone mineral density (BMD) in Korean postmenopausal women.

METHODS: Seven polymorphisms (rs2023239, rs806379, rs12720071, rs1049353, rs806368, rs2180619, and rs7766029) in the cannabinoid receptor type 1 (CNR1) gene and 16 polymorphisms (rs2501432, rs2502992, rs2501431, rs3003336, rs4649124, rs2502993, rs2229579, rs2229580, rs2229581, rs2229583, rs2229584, rs2229585, rs2229586, rs4237, rs7530595, and rs16828926) in the cannabinoid receptor type 2 (CNR2) gene were analyzed in 405 Korean postmenopausal women. Serum levels of bone turnover markers, osteoprotegerin (OPG), and soluble receptor activator of nuclear factor-κB ligand (sRANKL) were measured, and BMD at the lumbar spine and femoral neck was examined.

RESULTS: The CNR2 rs2501431, rs3003336, rs2229579, and rs4237 polymorphisms in CNR genes were associated with lumbar spine BMD. Women with the AA genotype of rs3003336 and rs4237 polymorphisms had significantly lower lumbar spine BMD compared with women with the non-AA genotype. Lumbar spine BMD in women with the TT genotype of CNR2 rs2501431 and rs2229579 polymorphisms was significantly lower than that in women with the non-TT genotype. Significantly higher odds for osteoporosis of the lumbar spine and/or femoral neck were observed in women with the TT genotype of rs2229579 polymorphisms (odds ratio, 3.43; 95% CI, 1.28-9.19) and with the AA genotype of rs4237 polymorphisms (odds ratio, 1.74; 95% CI, 1.03-2.95) compared with those not carrying the genotypes. The adjusted serum levels of bone turnover markers, OPG, sRANKL, or sRANKL × 1,000-to-OPG ratios were not associated with CNR gene polymorphisms.

CONCLUSIONS: Our results suggest that rs2501431, rs3003336, rs2229579, and rs4237 polymorphisms in CNR genes may be genetic factors affecting BMD in Korean postmenopausal women.