Association Between Circulating Inflammatory Cytokines and Dentofacial Anomalies

Introduction and aims: Previous studies have shown that some inflammatory cytokines are associated with dentofacial anomalies (DA), but the causal relationship is unclear. Therefore, the present study aimed to elucidate the relationship between circulating inflammatory cytokines, and DA risk by Mendelian randomization analysis.

Methods: A two-way two-sample Mendelian randomization analysis was used in our study. Data on 91 inflammatory cytokines were sourced from genome-wide association studies encompassing 14,824 participants across 11 distinct cohorts and protein quantitative trait loci from deCODE (35,559 participants). Summary statistics for DA were acquired from the FinnGen consortium (9254 cases and 245,664 controls). The inverse variance weighting method was used as the primary analysis, supplemented by a series of sensitivity analyses to determine the robustness and reliability of our findings.

Results: The analysis identified five cytokines - chemokine ligand 25, interleukin (IL)-10 receptor beta, IL-20, and stem cell factor - as inversely related to DA prevalence. Additionally, DA was associated with decreased levels of fibroblast growth factor (FGF)-19 and IL-24, and increased levels of FGF-23 and urokinase-type plasminogen activator. These findings were validated using protein quantitative trait loci data.

Conclusion: Our study substantiates an association between inflammatory cytokines and DA, emphasizing inflammation's pivotal role in the aetiology of DA.

Clinical significance: The findings provide a plausible genetic underpinning for the role of inflammation in DA, offering novel avenues for the development of targeted diagnostic and therapeutic strategies.