Vitamin D receptor gene ApaI polymorphism and susceptibility to osteoporosis in postmenopausal women: A meta-analysis from 22 Studies. Running title: VDR ApaI gene polymorphism and Osteoporosis

Objective: The ApaI polymorphism (G>T, rs7975232) of the vitamin D receptor (VDR) gene is located at the 3’-untranslated end, which does not alter the amino acid sequence of the encoded protein but influences gene expression, regulating mRNA stability[1, 2]. Although the role of ApaI in the risk of postmenopausal osteoporosis has been widely researched, the current results have yielded conflacts. Therefore, we performed an updated pooled analysis to provide comprehensive data on the association between VDR ApaI polymorphism and postmenopausal osteoporosis risk. Methods: : The PubMed, EMBASE, Weipu, CNKI, and Wanfang databases were searched for eligible studies from the database establishment to August 2021. Articles on the relationship between VDR gene ApaI polymorphism and osteoporosis were searched from the database. Case-control studies containing available genotype frequencies of A/a were chosen. The Newcastle-Ottawa quality assessment scales (NOS) standard was used to evaluate the quality of the literatures that met the inclusion and exclusion criteria. The odds ratio (OR) value with 95% confidence interval (95% CI) was used to assess the strength of this association. According to the heterogeneity, the fixed-effect model or random-effect model was used to combine the effect amount. Results: : 22 studies assessed the relationship between ApaI polymorphism and the risk of osteoporosis in postmenopausal women. The comprehensive analyses showed no significant association for ApaI polymorphism with postmenopausal osteoporosis in the overall population, equally valid for Asian and Caucasian subgroups with any genetic model. Conclusion: The present meta-analysis suggests that the VDR ApaI genotype may not affect the risk of postmenopausal osteoporosis in Asians and Caucasians. This is the latest period meta-analysis for the associations between VDR ApaI polymorphism and postmenopausal osteoporosis, as far as we know.