Genetic and epigenetic contributions to psychosomatic conditions in temporomandibular disorder: a systematic review

Temporomandibular disorder (TMD) is a complex condition with unclear causes and an uncertain diagnosis. Evidence suggests that genetic and epigenetic factors contribute to its pathogenesis and influence psychosomatic conditions. Understanding these genotype-phenotype interaction is crucial for improving diagnosis and developing targeted therapies. This systematic review aims to (i) examine the genetic and epigenetic factors involved in TMD and (ii) assess their association with psychosomatic manifestations. This review was registered in International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42024583915) and conducted in accordance with PRISMA guidelines. A systematic search of PubMed, MEDLINE, Scopus, ScienceDirect, Web of Science and Wiley databases identified studies published between 2019 and 2024. Eligible studies were selected based on predefined inclusion criteria. Extracted genomic and epigenomic data were analysed to identify predictive and diagnostic markers associated with TMD. A decision matrix analysis was performed to determine the most significant factors. Ten studies met the inclusion criteria. Genetic variations associated with TMD encode for structural, transporter, regulatory, receptor, enzymatic and ion channel proteins, while epigenetic modifications affected genes encoding extracellular protein, enzyme and transcription factor. Among these, COMT rs4680 was the most extensively studied, showing strong associations with pain modulation and anxiety in TMD patients.