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Background  Several studies have been performed to investigate association between IL-6 174G/C (rs1800795) and 572C/G (rs1800796) gene polymorphisms and osteoporosis predisposition. However, the results were conflicting. So, we performed a meta-analysis designed to provide more reliable results for the association between IL-6 gene polymorphisms and osteoporosis.    Methods  Studies were searched using PubMed, EMBASE, the Cochrane Library and Wanfang electronic databases. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between IL-6 174G/C (rs1800795) and 572C/G (rs1800796) gene polymorphisms and osteoporosis risk. The false-positive report probabilities (FPRP) test and the venice criteria were used to assess the credibility of statistically significant associations.    Results  A total of 9 studies with 1891 osteoporosis patients and 2027 healthy controls were included in current meta-analysis. Overall, The IL-6 174G/C (rs1800795) gene polymorphism was insignificantly associated with osteoporosis vulnerability. For IL-6 572C/G (rs1800796), statistically significant elevated osteoporosis vulnerability was found in IL-6 572C/G additive model (OR = 2.25, 95% CI: 1.55–3.26), dominant model (OR = 1.42, 95% CI: 0.78–2.56) and recessive model (OR = 1.96, 95% CI: 1.36–2.83). However, the IL-6 572C/G C allele was found to be associated with reduced susceptibility to osteoporosis (OR = 0.76, 95% CI: 0.56–1.04). When excluding studies that did not conform to HWE, the results did not change significantly. Further, when we evaluated the credibility of the positive results of the current meta-analysis, we identified less credible positive results in IL-6 572C/G recessive and additive model.    Conclusion  In conclusion, IL-6 572C/G GG genotype may be associated with increased risk of osteoporosis.

Association of IL-6 174G/C (rs1800795) and 572C/G (rs1800796) polymorphisms with risk of osteoporosis: a meta-analysis