Causal Association Between Transferrin Saturation and Periodontitis: A Mendelian Randomization Study

Iron deficiency anemia may influence the development of periodontitis bidirectionally. This study aimed to examine the causal association of iron deficiency anemia and iron status on the occurrence of periodontitis predicted through Mendelian randomization (MR) analysis.

This two-sample MR study used summary data from large-scale genome-wide association studies of iron deficiency anemia (obtained through the meta-analysis of two large datasets), iron status, and periodontitis. Analysis was conducted using inverse variance weighted (IVW) as the main analysis and with weighted median, weighted mode, and MR-Egger regression methods as complementary analyses. Sensitivity analyses were evaluated using Cochran's Q-test, MR-Egger regression, MR-PRESSO analysis, and leave-one-out analysis to assess the robustness and consistency of the results.

Genetic predictions indicated a statistically significant association between transferrin saturation as the exposure and periodontitis as the outcome (OR=1.23, 95%CI: 1.08-1.41, p=0.002). No causal associations were observed between the other exposures (iron deficiency anemia, serum iron, serum ferritin, and TIBC) (all p>0.05). Cochran's Q-test showed no statistically significant heterogeneity, and the MR-Egger regression results suggested that this analysis was not influenced by horizontal pleiotropy. The MR-PRESSO results indicated that there were no outliers.

The results suggest the presence of a positive causal association between transferrin saturation and periodontitis, but not iron deficiency anemia, serum iron, serum ferritin, and TIBC as exposures. Hence, the findings provide genetic evidence that anemia may be a potential cause for periodontitis, suggesting that attention to and management of patients' systemic hematological status may be important in the prevention and comprehensive treatment of periodontal disease.