Associations of LRP5 Gene With Bone Mineral Density, Bone Turnover Markers, and Fractures in the Elderly With Osteoporosis

Abstract

The study aimed to explore the associations of rs4988300 and rs634008 in the low-density lipoprotein receptor-related protein 5 (LRP5) gene with bone mineral density (BMD), bone turnover markers (BTM), and fractures in elderly patients with osteoporosis (OP). Methods: Our study included 328 unrelated OP patients with or without fractures. Genomic DNA was extracted for genotyping. BTM levels were assessed by electrochemiluminescence (ECL). Dual-energy X-ray absorptiometry (DXA) was employed to measure BMD in the lumbar spine (LS) and proximal femur. Basic features between the OP and fracture groups were analyzed using the t-test. The Chi-square test was performed to analyze the differences in allele and genotype frequencies. The associations of single-nucleotide polymorphisms (SNPs) with BMD and BTM in the subgroups were investigated by the analysis of covariance (ANCOVA) adjusted for confounding factors. Results: In both females and males, individuals with fractures exhibited higher BTM levels and lower BMD values than those with OP (P < 0.05). The allele and genotype frequencies of rs4988300 in the subgroups were significantly different (P < 0.05). In both females and males suffering from OP, participants with rs4988300 GG or rs634008 TT presented lower procollagen I N-terminal propeptide (PINP) levels (P < 0.05). Women with OP carrying rs4988300 GG exhibited lower BMD values at FN and TH (P < 0.05). In both females and males with fractures, individuals carrying rs4988300 GG genotype or rs634008 TT genotype exhibited lower PINP levels and BMD values at FN and TH than those with other genotypes (P < 0.05). Conclusions: Rs4988300 and rs634008 polymorphisms in the LRP5 gene are associated with bone phenotypes in the elderly with OP or fractures.

[Retracted] Effects of Stress on Osteoblast Proliferation and Differentiation Based on Endoplasmic Reticulum Stress and Wntβ‐Catenin Signaling Pathway

“…Present studies showed that the low-density lipoprotein receptor-associated protein 5 (LRP5) in the Wnt signaling pathway is closely related to the progression of osteoporosis [9]. Moreover, many studies suggested that LRP5 is closely related to bone metabolism [10][11][12]. However, it is still unclear whether the Wnt signaling pathway can participate in the biomechanical signaling process.…”

17 variants interaction of Wnt/β-catenin pathway associated with development of osteonecrosis of femoral head in Chinese Han population

“…Therefore, the associations between the variants of LRP5 gene and BMD or osteoporotic fractures have been extensively explored. Rs4988300 and rs634008 of LRP5 gene also associated with bone phenotypes in the elderly with OP or fractures 33 .To our knowledge, the association of the four variants of LRP5 with the development of ONFH was for the first time reported in this study.…”

The role of LRP5-LRP6 gene-gene and gene-environment interactions on the risk of ABM in postmenopausal women with type 2 diabetes mellitus

“…OP is a chronic metabolic disease with reduced BMD as the primary manifestation and a severe threat to the population's health [12]. Numerous studies have shown that genetic polymorphisms are closely associated with the occurrence of OP [13][14]. Therefore, further investigation of the pathogenesis of OP at the gene level may provide a theoretical basis to explain the occurrence of OP [15].…”