Evaluation of common variants in the CNR2 gene and its interaction with abdominal obesity for osteoporosis susceptibility in Chinese post-menopausal females

Abstract

ObjectivesThe objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.MethodsChinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (http://analysis.bio-x.cn/) was employed.ResultsThe logistic regression model revealed that the C allele of rs2501431 and the G allele of rs3003336 were associated with increased OP risk, compared with those with wild genotype. However, no significant correlations were found when analyzing the association of rs4237 and rs2229579 with OP risk. The GMDR analysis suggested that the interaction model composed of two factors, rs3003336 and abdominal obesity (AO), was the best model with statistical significance (p-value from sign test (Psign) = 0.012), indicating a potential gene-environment interaction between rs3003336 and AO. Overall, the two-locus models had a cross-validation consistency of 10/10 and had a testing accuracy of 0.641. Abdominally obese subjects with the AG or GG genotype have the highest OP risk, compared with subjects with the AA genotype and normal waist circumference (WC) (odds ratio (OR) 2.23, 95% confidence interval (CI) 1.54 to 3.51). Haplotype analysis also indicated that the haplotype containing the rs3003336-G and rs2501431-C alleles was associated with a statistically increased OP risk.ConclusionOur results suggested that the C allele of rs2501431 and the G allele of rs3003336 of the CNR2 gene, interaction between rs3003336 and AO, and the haplotype containing the rs3003336-G and rs2501431-C alleles were all associated with increased OP risk.Cite this article: Bone Joint Res 2019;8:544–549.

Pharmacological Properties, Therapeutic Potential and Molecular Mechanisms of JWH133, a CB2 Receptor-Selective Agonist

“…Preclinical studies revealed that CB2R-knockout mice developed osteoporosis at 12 months, reduced osteoblast production and function, and enhanced osteoclast production (Sophocleous et al, 2011). Clinical studies of postmenopausal women demonstrated that the gene encoding the CB2R (CNR2) is responsible for low bone mineral density (Zheng et al, 2019). Thus, CB2Rs may be a translational target for pharmacologic agents that augment bone regeneration, but quality clinical trials are warranted.…”

Gut microbiome and osteoporosis

“… 1 Heredity, hormone levels, nutrition, and lifestyle are closely related to the pathogenesis of OP. 2 - 4 Oestrogen, parathyroid hormone, vitamin D, and inflammatory factors are all important regulators of bone metabolism. Although many aetiologies have been identified, the pathogenesis of OP is still being explored.…”

The Role of Endocannabinoid System in Menopause and Its Related-Diseases

“…Obesity has an impact on the relationship between CB2 gene SNPs and Osteoporosis (OP) risk [40,41]. It has been demonstrated that the CB2 variant rs3003336 is associated to abdominal obesity in obese post-menopausal women which showed an increased risk of OP onset [30].…”