Association between OPG polymorphisms and osteoporosis risk: An updated meta-analysis

Abstract

Background: Numerous studies have demonstrated an association between osteoprotegerin (OPG) polymorphisms (A163G (rs3102735), T245G (rs3134069), T950C (rs2073617), G1181C (rs2073618)) and osteoporosis risk. However, their conclusions are inconsistent. In addition, some new studies have been updated, and more importantly, previous meta-analyses have not tested for false-positive results. In order to further explore these associations, we recently conducted a meta-analysis.Objectives: To study the relationship between OPG polymorphisms A163G, T245G, T950C, G1181C and the risk of osteoporosis.Methods: PubMed, Medline, International Statistical Institute (ISI), China National Knowledge Infrastructure (CNKI) and China Wanfang Database were used for research searches. Associations were assessed with five genetic models using odds ratios (ORs) with 95% confidence intervals (CIs). In addition, confidence in statistically significant associations was assessed using false-positive report probability (FPRP), Bayesian probability of False discovery (BFDP), and Venice criteria.Results: On the whole, the OPG A163G polymorphism was not significantly associated with risk of osteoporosis. However, in a subgroup analysis, we found that the OPG A163G polymorphism increased the risk of osteoporosis in Caucasians (AG + GG vs AA: OR = 1.35, 95% CI = 1.06–1.73; AA + GG vs AG: OR = 0.64, 95% CI = 0.49–0.82) and the female (G vs A: OR = 1.30, 95% CI = 1.03–1.64; AG + GG vs AA: OR = 1.42, 95% CI = 1.18–1.71). At the same time, the OPG G1181C polymorphism reduces the risk of osteoporosis (C vs G: OR = 0.84, 95% CI = 0.74–0.95; CC vs GG: OR = 0.75, 95% CI = 0.60–0.93; GC + CC vs GG: OR = 0.80, 95% CI = 0.67–0.95; CC vs GG + GC: OR = 0.84, 95% CI = 0.70–1.00). Moreover, a significantly decreased risk of osteoporosis was also discovered in Asian (C vs G: OR = 0.80, 95% CI = 0.66–0.98; CC vs GG: OR = 0.67, 95% CI = 0.47–0.95; GC + CC vs GG: OR = 0.74, 95% CI = 0.58–0.95) and the female (C vs G: OR = 0.85, 95% CI = 0.75–0.97; CC vs GG: OR = 0.77, 95% CI = 0.61–0.96; GC + CC vs GG: OR = 0.79, 95% CI = 0.66–0.95). Finally, we did not find a close association between OPG T245G and T950C polymorphisms and osteoporosis risk. However, when we retained only studies in the control group that was consistent with Hardy-Weinberg equilibrium (HWE) and high-quality scores, we observed that the OPG A163G polymorphism increased the risk of osteoporosis in the overall analysis (G vs A: OR = 1.40, 95% CI = 1.16–1.68; GG vs AA: OR = 1.96, 95% CI = 1.20–3.21; AG + GG vs AA: OR = 1.45, 95% CI = 1.22–1.72). Finally, after the credibility assessment, we concluded that all statistically significant association results in the meta-analysis in this study and those in the previous study were ‘positive results with low confidence’.Conclusion: In conclusion, our study concluded that all meaningful results between OPG A163G and G1181C polymorphisms and osteoporosis risk were false-positive results rather than true associations.

Osteoprotegerin Gene as a Biomarker in the Development of Osteoporosis in Postmenopausal Women

“…A meta-analysis conducted in 2022 by Han et al, taking into account all studies conducted to date, also found no effect of the osteoprotegerin rs3134070 polymorphism on the incidence of osteoporosis, which is in line with the conclusions drawn from this study [10].…”

“…A comprehensive meta-analysis performed in 2022 by Han et al, where they analyzed the results of most of the above studies as well as previously performed meta-analyses, showed that all significant associations between OPG rs3102735 polymorphisms and increased osteoporosis risk tended to be false positives, which is in line with the results obtained in this paper [10].…”

“…However, the authors themselves acknowledge that, due to the limitations of this study, the results and conclusions presented should be interpreted with caution [38]. Also, a metaanalysis by Han et al considering 12 studies, including 1610 cases and 1234 controls, and previous meta-analyses found no statistically significant correlation between the rs207361 polymorphism and osteoporosis [10].…”

“…Due to the role of osteopotegrin in the bone formation process, numerous polymorphisms of the OPG gene have become the subject of research regarding their impact on BMD (rs2073618, rs3102735) [9], the risk of osteoporosis (rs3102735, rs2073618) [10], and the response to treatment in postmenopausal osteoporosis (rs3102735, rs2073618) [11]. However, the data are often ambiguous, or even contradictory, and do not include Caucasians.…”

Association between the ESR1 and ESR2 polymorphisms and osteoporosis risk: An updated meta-analysis

“…The evaluation criteria of studies quality were shown in Table S1, Supplemental Digital Content, http://links.lww.com/MD/K138 according to previous studies. [ 53 – 55 ] Two authors assessed the studies quality, respectively. The total score was 21 points, studies scoring > 13 were high quality.…”