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Background  Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis.    Methods  Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated.    Results  Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01–46.06,  P  < 0.001; SMD = 2.25, 95% CI = 1.25–3.24,  P  < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups ( P  = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion.    Conclusions  High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12950-021-00281-9.

VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation