High level of HE4 was positively associated with Stage III/IV periodontitis in the different models: Crude model (ORtertile3vs1 = 5.03, 95% CI: 3.22–8.14), Model I (ORtertile3vs1 = 3.33, 95% CI: 2.05–5.56) and Model II (ORtertile3vs1 = 2.35, 95% CI: 1.35–4.21). This evidence concerns the gene WFDC2 and periodontitis.