Exploring Relationships Between Circulating Interleukins and Pulp and Periapical Diseases: A Bidirectional Mendelian Randomization Study

Introduction: The aim of this study was to comprehensively evaluate the links of genetic predisposition among 13 common circulating interleukins (ILs) and endodontic diseases by using a 2-sample Mendelian randomization method. Methods: Single nucleotide polymorphisms were chosen as instrumental variables from summary data of genome-wide association studies (GWASs), using the inverse-variance-weighted method as the primary analysis. In addition, a variety of sensitivity analyses was conducted to evaluate the resilience of the primary outcomes and identify any inherent pleiotropic effects. Results: After multiple comparison corrections, 4 circulating ILs were genetically predicted to significantly play a role in endodontic diseases. Among these, circulating IL-17 (odds ratio [OR](IVW), 1.33; 95% confidence interval [CI], 1.15-1.54; P < 3.85 x 10(-3)) were significantly identified as potential risk-increasing factors toward pulp and periapical diseases, and circulating IL-16 (ORIVW, 0.89; 95% CI, 0.83 to 0.94; P < 3.85 x 10(-3)) may exert protective effects on the development of periapical abscess. In the reverse analyses, null significantly association was found between genetic liability to endodontics disorders and the corresponding circulating inflammatory biomarkers. Overall, sensitivity analyses were consistent with the estimates direction of primary analyses results, supporting the reliability of findings. Conclusions: Given the unavoidable limitations presented in this study, our findings provided significant evidence to support the identification of elevated IL-16 levels as a potential risk-mitigating factor, whereas elevated IL-17 levels exhibit potentially deleterious effects on endodontic disorders. Future validation is warranted to examine the conclusions of our study and to evaluate the potential application of these circulating ILs as lifestyle or pharmacological targets for oral health care.