GENETIC DETERMINANTS OF TEMPOROMANDIBULAR JOINT DISORDERS AND THEIR IMPLICATIONS FOR PROSTHODONTIC REHABILITATION

Abstract

Background: Temporomandibular disorders (TMDs) are multifactorial conditions in which genetic susceptibility may interact with clinical and behavioral factors. The contribution of specific genetic polymorphisms to TMD occurrence and response to prosthodontic rehabilitation remains incompletely characterized. Aim: To evaluate the association of selected genetic polymorphisms, including catechol-O-methyltransferase (COMT), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), matrix metalloproteinase-1(MMP1), and Estrogen Receptor 1/ Estrogen Receptor 2 (ESR1/ESR2), with TMD status and to assess whether these variants were associated with changes in pain intensity and maximum mouth opening following prosthodontic rehabilitation Methods: The study included 120 participants, comprising 80 individuals with TMDs and 40 healthy controls. Demographic and clinical characteristics were assessed, including symptom duration, maximum unassisted mouth opening, visual analog pain (VAS) pain scores, joint sounds, muscle tenderness, TMJ tenderness, and mandibular movement. The distribution of selected genetic variants was compared between the TMD and control groups. Multivariable logistic regression was performed to identify factors independently associated with TMD. Changes in VAS pain scores and maximum mouth opening following prosthodontic rehabilitation were additionally compared according to genetic variant status. Results: Among participants with TMDs, the mean symptom duration was 3.42 ± 2.71 years, maximum unassisted mouth opening was 38.74 ± 6.21 mm, and mean VAS pain score was 5.21 ± 1.84. Myofascial pain was the most frequent TMD subtype (42.5%). Variant genotypes were more frequently observed in the TMD group than among controls for COMT (48.8% vs. 30.0%; probability (p) =0.033), TNF-α (43.8% vs. 25.0%; p=0.021), IL-10 (40.0% vs. 22.5%; p=0.037), and MMP1 (38.8% vs. 20.0%; p=0.014). Multivariable analysis demonstrated significant associations of TMD with COMT variant status (adjusted odds ratio (OR)=2.31; 95% confidence interval (CI): 1.14–4.69;p =0.020), TNF-α variant status (adjusted OR=2.08; 95% CI: 1.02–4.25; p=0.043), MMP1 variant status (adjusted OR=2.76; 95% CI: 1.18–6.47; p=0.019), and parafunctional habits (adjusted OR=2.44; 95% CI: 1.22 4.89; p=0.011). Age and female sex were not independently associated with TMD. None of the evaluated polymorphisms was significantly associated with the reduction in VAS pain scores or improvement in maximum mouth opening following rehabilitation (all p>0.05). Conclusion: The findings demonstrate associations between selected COMT, TNF-α, and MMP1 genetic variants and TMD status, alongside an association with parafunctional habits. However, genetic variant status was not significantly related to the magnitude of symptomatic or functional improvement following prosthodontic rehabilitation. These findings support a potential role of genetic susceptibility in TMD occurrence while emphasizing that the observed associations should not be interpreted as evidence of causation.