Associations between ERα/β gene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women: a systematic review and meta-analysis

Abstract

BackgroundMany studies have reported associations between estrogen receptor (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone mineral density (BMD), but the results are controversial. The aim of the present meta-analysis is to verify the association between ERα and ERβ gene polymorphisms and osteoporosis susceptibility and BMD in postmenopausal women.MethodsPubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu Library were searched. OR and WMD with 95% CI were calculated to assess the association.ResultsOverall, no significant association was observed between ERα XbaI, ERα PvuII and PMOP susceptibility in either overall, Caucasian or Asian populations. ERα G2014A was significantly associated with a decreased risk of PMOP in Caucasian populations. There was a significant association between ERβ RsaI and PMOP risk in both overall and Asian populations. Caucasian PMOP women with ERα XbaI XX and Xx genotypes had a higher LS Z value than women with xx genotype. ERα XbaI XX genotype was associated with increased FN BMD in overall and Caucasian populations, an increased FN Z value in Asians, and a decreased FN Z value in Caucasians. There was also a significant association between ERα XbaI Xx genotype and an increased FN Z value in either Asians or Caucasians. ERα PvuII PP genotype was associated with a low LS Z value in Caucasians and a low FN BMD and Z value in Asians. Pp genotype in PMOP women was significantly correlated with low LS BMD in overall populations, a low FN Z value in either overall, Caucasian or Asian populations.ConclusionEach ERα and ERβ gene polymorphism might have different impact on PMOP risk and BMD in various ethnicities.

The estrogen receptor 1 gene affects bone mineral density and osteoporosis treatment efficiency in Slovak postmenopausal women

“…A meta-analysis of 30 studies published by Ioannidis et al [ 33 ] showed a positive effect of GG genotype on BMD and fracture risk, whereas rs2234693 polymorphism was not associated with these traits. In a recent review and meta-analysis of Zhu et al [ 34 ] the authors found significant associations of ESR1 polymorphisms with BMD in Caucasian women. The GG and AG genotypes were associated with increased FN BMD and FN Z value, respectively.…”

Decisive gene strategy on osteoporosis: a comprehensive whole-literature-based approach for conclusive candidate gene targets

“…After menopause, the reduced ovarian synthesis of estrogen in women results in bone loss, thereby causing osteoporosis [ 29 ]. Additionally, estrogen is a regulator of bone metabolism, and a reduction in estrogen concentration results in BMD loss, increased mechanical loading, induced bone remodeling, and postmenopausal osteoporosis development [ 30 , 31 ]. It has been demonstrated in studies on mice that the functional ESR and Wnt/β-catenin signaling pathways interact in regulating bone mass adaptation in response to mechanical loading [ 32 ].…”

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

“…The pathogenesis of OP is largely determined by genetic factors. Numerous studies have demonstrated that genetic variances in the estrogen receptor (ER) gene (21,22), vitamin D receptor (VDR) gene (23,24), and genes of the RANKL-RANK-OPG system (25) are implicated in regulating bone metabolism and influencing bone mass. Additionally, LRP5, a co-receptor of the Wnt pathway, was previously reported as a potential factor in the development of OP (26).…”