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Background and Objective  Genetic factors are important in the pathogenesis of fractures. Notably, estrogen receptor α ( ESR1 ) has been suggested as a possible candidate gene for hip fractures; however, published studies of  ESR1  gene polymorphisms have been hampered by small sample sizes and inconclusive or ambiguous results. The aim of this meta-analysis is to investigate the associations between two novel common  ESR1  polymorphisms (intron 1 polymorphisms PvuII-rs2234693: C>T and XbaI-rs9340799: A>G) and hip fracture.    Methods  Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association.    Results  Five case-control and three cohort studies were assessed, including a total of 1,838 hip fracture cases and 14,972 healthy controls. This meta-analysis revealed that the PvuII T allele is a highly significant risk factor for hip fracture susceptibility, with an effect magnitude similar in male and pre-menopausal and post-menopausal female patients. In stratified analysis based on ethnicity, the PvuII T allele remained significantly correlated with increased risk of hip fracture in Caucasian populations; this correlation, however, was not found in Asian populations. Unlike the PvuII polymorphism, we did not find significant differences in the XbaI (A>G) polymorphism allele or genotype distributions of hip fracture patients and controls. We also found no obvious association between the XbaI polymorphism and hip fracture in any of the racial or gender subgroups.    Conclusion  Our findings show that the  ESR1  PvuII T allele may increase the risk of hip fracture and that the XbaI polymorphism is not associated with hip fracture.

Association between Estrogen Receptor α Gene (ESR1) PvuII (C/T) and XbaI (A/G) Polymorphisms and Hip Fracture Risk: Evidence from a Meta-Analysis