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Aim: To investigate the potential impact of genetic background on treatment outcomes in patients with temporomandibular disorders (TMD). Materials and Methods: Sixty TMD patients diagnosed with painful TMD (according to DC/TMD) were treated with stabilization splints. Genomic DNA was extracted from buccal swabs and analyzed for polymorphisms: rs4818, rs6269 in the catechol-O-methyltransferase (COMT) gene, and rs1387964 in the opiorphin (OPRPN) gene. Treatment outcomes, assessed at baseline and after 6 months of treatment, included a range of mouth opening, level of jaw limitation, pain intensity (measured with Graded Chronic Pain Scale_GCPS and Visual Analogue Scale_VAS), anxiety, and depression. Mann-Whitney U test was used to compare changes in treatment outcomes between different genotypes. Results: Dominant and recessive genetic models were used in the assessment. In both models, the minor allele represented the risk allele. A recessive model estimated the effect of being homozygous with the minor allele and the dominant model estimated the effect of carrying one or both minor alleles.”Patients carrying two copies of the minor allele of rs1387964 (CC genotype) reported significantly less pain reduction than patients carrying the other two genotypes (GCPS: p=0.02 ; VAS: p=0.04). Patients carrying one or two copies of the minor allele of rs4818 (CG+GG) exhibited less reduction of jaw functional limitation (mastication, p=0.03) and less improvement of mouth opening (p |