Genetic influence on treatment outcomes in patients with pain-related temporomandibular disorders.

BACKGROUND: Single nucleotide polymorphisms (SNPs) may influence pain susceptibility and impact treatment response in pain-related temporomandibular disorders (TMDp). OBJECTIVE: Explore the role of COMT (rs4646310, rs6269, rs4818, rs4680) and OPRM1 (rs1799971) genotypes in regulating treatment response. METHODS: Sixty TMDp patients (55 females and 5 males), diagnosed with the Diagnostic Criteria for TMD (DC/TMD), underwent standardised treatment (information and education, home physical therapy, occlusal splint) for 6 months. Treatment outcomes included: pain intensity, pain-free mouth opening, jaw functional limitation, depression, and anxiety. Genotyping for COMT and OPRM1 SNPs was performed using DNA from buccal mucosa swabs and TaqMan assays. Statistical analysis was carried out to compare the changes in treatment outcomes and the influence of genotypes on treatment response. RESULTS: Significantly less pain reduction was observed in minor allele carriers of rs4646310, and rs4680 compared to dominant homozygous (p < .025). Minor allele carriers of rs1799971 and rs4646310 demonstrated worsening in pain-free mouth opening while dominant homozygous exhibited improvement (p < .025). Significantly less anxiety reduction was observed in minor allele carriers of rs4646310 compared to dominant homozygous (p = .003). Of the all variables assessed in the regression model, carrying a minor allele of rs1799971 predicted a poorer treatment response considering pain-free mouth opening while carrying a minor allele of rs4646310 predicted less pain and less anxiety reduction. CONCLUSION: Our findings indicate that certain SNP variants of the COMT and OPRM1 genes were associated with poorer treatment response and may therefore play a significant role in the classification of TMDp patients. Also, assessment of patient genotype could potentially aid in predicting treatment response.

Association of oral behaviours and psychological factors with selected genotypes in pain-related TMD.

OBJECTIVES: To investigate frequency of single nucleotide polymorphisms (SNPs) in pain-related temporomandibular disorders (TMDp) and to determine whether specific SNPs, psychological, psychosomatic and behavioural characteristics are predictive for pain existence and intensity (low pain intensity (LPI)/high pain intensity (HPI)). METHODS: Genomic DNA was extracted from buccal mucosa swabs (85 TMDp;85 controls) for evaluating frequency of selected SNPs: catechol-O-methyltransferase (rs4680, rs4818), opiorphin (rs1387964), alpha subunit of voltage-gated sodium channel Nav1.1 (rs6432860) and voltage-gated sodium channel Nav1.9 (rs33985936). Participants completed questionnaires on somatosensory amplification, anxiety and depression symptoms and oral behaviours (OB). RESULTS: Sleep-related OB frequency was higher in TMDp patients compared to controls (p = 0.008). Compared to LPI, HPI patients had higher depression (p = 0.020) and anxiety scores (p = 0.017). TMDp group showed higher frequency of CC genotype (rs1387964) than controls (12.9% vs. 3.5%, p = 0.025). Following adjustments for age, sex and sleep-related OB, the significance of the recessive model (CC vs. TC + TT) between TMDp patients and controls was retained (OR = 5.783; 95%CI: 1.454-23.004). Frequency of GG genotype (rs4680 and rs4818) was higher in HPI compared to LPI patients (40% vs. 11.4%, p = 0.006; 24% vs. 3%; p = 0.012, respectively). The difference remained significant after adjusting for age, sex, depression, anxiety and sleep-related OB (rs4680: OR = 3.621; 95%CI: 1.580-8.297; rs4818: OR = 4.919, 95%CI: 1.641-14.746). CONCLUSION: This study has demonstrated that rs1387964 CC genotype was associated with TMDp while rs4680 GG and rs4818 GG genotypes contributed to HPI.