Effect of type 1 diabetes on oral lichen planus mediated by IL-10

Abstract

Background: While observational studies have highlighted a potential link between diabetes and oral lichen planus (OLP), the causal relationship remains unclear, and it is uncertain which specific form of diabetes might promote OLP development. This Mendelian randomization (MR) study aims to estimate the causal effects of diabetes-related traits on OLP and identify potential mediating factors. Methods: Utilizing summary statistics from genome-wide association studies predominantly of European ancestry, we conducted univariable and multivariable MR to estimate overall and independent effects of four diabetes-related traits (type 1 diabetes [T1D], type 2 diabetes [T2D], fasting glucose, fasting insulin) on OLP. Two-step MR was employed to identify and assess the mediation proportion of 91 inflammatory factors. Results: Genetic susceptibility to T1D was found to increase the risk of OLP (inverse-variance weighted OR: 1.10, 95% CI: 1.04–1.16, p = 0.002), with consistent findings across all MR methods. The relationship between T1D and OLP remained robust after adjusting for T2D, fasting insulin, and fasting glucose. Furthermore, IL-10 was identified as a partial mediator, accounting for 23.3% of the causal effect of T1D on OLP. No potential pleiotropy for significant estimates was detected (p > 0.05). Univariable MR analyses showed no significant causal relationship between T2D, fasting glucose, fasting insulin, and OLP development. Conclusions: IL-10 may partially mediate the association between T1D and OLP. These findings provide genetic evidence suggesting a potential link between T1D and OLP through pathways beyond glycemic regulation, but should be interpreted with caution given the limitations of the study.