Association of ESR1 and ESR2 Polymorphisms with Osteoporosis: A Meta-Analysis from 36 Studies

Background: Recently, the roles of ESR1 and ESR2 polymorphisms in osteoporosis have been extensively reported, with conflicting findings. Therefore, we performed this present study to evaluate the potential associations between ESR1 and ESR2 polymorphisms and osteoporosis risk. Methodology: All included literatures published up to April 2021 were identified by searching Pubmed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated the associations using a fixed or random effects model. Results: 36 observational studies involving five gene polymorphisms (ESR1 PvuII, ESR1 XbaI, ESR1 G2014A, ESR2 AluI and ESR2 RsaI) covering 12507 cases and 18487 controls were included. The results of our meta-analysis demonstrated the variant A allele of ESR2 RsaI polymorphism might play a remarkable protective role in developing osteoporosis under all genetic models. However, no associations were observed between ESR1 PvuII, ESR1 XbaI, ESR1 G2014A and ESR2 AluI polymorphisms with the risk of osteoporosis under all genetic models. Conclusions: Our meta-analysis suggests that genetic polymorphism in ESR2 RsaI may lead to decreased risk for osteoporosis. Further larger studies are needed to confirm this conclusion.