Purinergic P2X7 receptor functional genetic polymorphisms are associated with the susceptibility to osteoporosis in Chinese postmenopausal women

Abstract

Osteoporosis (OP) is a major public health problem worldwide. Genetic factors are considered to be major contributors to the pathogenesis of OP. The purinergic P2X7 receptor (P2X7R) has been shown to play a role in the regulation of osteoblast and osteoclast activity and has been considered as an important candidate gene for OP. A case-control study was performed to investigate the associations of functional single nucleotide polymorphisms (SNPs) in the P2X7R gene (rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143) with susceptibility to OP in 400 Chinese OP patients and 400 controls. Results showed that rs3751143 was associated with OP; in particular, carriers of the C allele and CC/(AC + CC) genotypes were at a higher risk of OP, but no significant association of rs2230911, rs7958311, rs1718119, and rs2393799 with OP risk was observed. Analysis of the haplotypes revealed one haplotype (rs1718119G-rs2230911G-rs3751143C) that appeared to be a significant Brisk^haplotype with OP. The rs3751143 polymorphism was associated with osteoclast apoptosis; ATP-induced caspase-1 activity of osteoclasts with AC and CC genotypes is lower than that of osteoclasts with AA genotype in vitro. The findings suggest that the P2X7R rs3751143 functional polymorphism might contribute to OP susceptibility in Chinese postmenopausal women.

The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis

“…OP, together with its main health outcome, which is fragility fractures, is a large and escalating global issue [1]. Efforts have been made to overcome this obstacle, and genetic factors are proposed to be major contributors to the pathogenesis of this disease [16]. The understanding of the genetic factors of OP is of crucial value for disease prevention [17] and for the search for novel therapies.…”

P2X7, a critical regulator and potential target for bone and joint diseases

“…Lossof-function polymorphisms in the P2X7 receptor gene may decrease the bone mineral density and the risk of vertebral fractures. Other studies also suggested that the polymorphisms of P2X7 receptor may increase the risk of developing osteoporosis in postmenopausal women (Gartland et al, 2012;Xu et al, 2017). Reduced or no function of the P2X7 receptor may lead to low lumbar spine bone mineral density and accelerated bone loss.…”

“…The activation of P2X7 receptor can relieve some bone disease such as osteoporosis and the stress fracture injury. There are some clinical evidence showed that P2X7 receptor rs3751143 functional genetic polymorphisms might contribute to osteoporosis in postmenopausal women (Xu et al, 2017). The knockout of P2X7 receptor gene can increase osteoclast numbers and osteoclast surface and leading to the decrease of trabecular bone mass in mouse (Ke et al, 2003).…”

Research progress on the P2X7 receptor in liver injury and hepatocellular carcinoma

“…The P2X7 receptor has more than 11 single nucleotide polymorphisms (SNP S ). These SNP S have important effects on P2X7 receptor function, and P2X7 receptor polymorphisms have clinical value in different diseases and tumors (including but not limited to tuberculosis (Alshammari et al, 2016), SLE complicated with pericarditis (Hu et al, 2020), rheumatoid arthritis (Bahari et al, 2021), osteoporosis (Xu et al, 2017), and cervical cancer (Yang et al, 2016)). Duan and his colleague selected 5 SNP S located in the P2X7 receptor from the Beijing Han HapMap database (dbSNP b126), namely rs2393799, rs28360457, rs3751143, rs1718119, and rs2230911.…”