ObjectivesTo 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)).MethodsGenomic 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).ResultsSleep‐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).ConclusionThis study has demonstrated that rs1387964 CC genotype was associated with TMDp while rs4680 GG and rs4818 GG genotypes contributed to HPI.

Microsatellite instability (MSI) represents an accumulation of frameshifts in short tandem repeats, microsatellites, across the genome due to defective DNA mismatch repair (dMMR). MSI has been associated with distinct clinical, histological, and molecular features of tumors and has proven its prognostic and therapeutic value in different types of cancer. Recently, another type of microsatellite instability named elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been reported across many different tumors. EMAST tumors have been associated with chronic inflammation, higher tumor stage, and poor prognosis. Nevertheless, the clinical significance of EMAST and its relation to MSI remains unclear. It has been proposed that EMAST arises as a result of isolated MSH3 dysfunction or as a secondary event in MSI tumors. Even though previous studies have associated EMAST with MSI-low phenotype in tumors, recent studies show a certain degree of overlap between EMAST and MSI-high tumors. However, even in stable tumors, (MSS) frameshifts in microsatellites can be detected as a purely stochastic event, raising the question of whether EMAST truly represents a distinct type of microsatellite instability. Moreover, a significant fraction of patients with MSI tumors do not respond to immunotherapy and it can be speculated that in these tumors, EMAST might act as a modifying factor.

The frequency of selected polymorphisms, one in each gene coding for proteins with antioxidative properties (CAT(rs1001179), SOD2(rs4880), GPX1(rs1050450), and NQO1(rs689452)), was compared between patients suffering from pain-related temporomandibular disorders (TMDp; n = 85) and control subjects (CTR; n = 85). The same was evaluated when participants were divided with respect to oral behavioural habits frequency into high-frequency parafunction (HFP; n = 98) and low-frequency parafunction (LFP; n = 72) groups. Another aim was to investigate whether polymorphisms in these genes can be associated with participants’ psychological and psychosomatic characteristics. Polymorphisms were genotyped using the genomic DNA extracted from buccal mucosa swabs and real-time TaqMan genotyping assays. No differences in genotype distribution between TMDp patients and control subjects were found. Still, TMDp patients who were homozygous for minor allele A, related to the GPX1 polymorphism rs1050450, reported significantly more waking-state oral behaviours than GA + GG genotype carriers (score: 30 vs. 23, p = 0.019). The frequency of genotype AA for rs1050450 polymorphism was higher in HFP than in LFP participants (14.3% vs. 4.2%, p  = 0.030). The most important predictors of waking-state oral behaviours were depression, anxiety, AA genotype (rs1050450), and female sex. The explored gene polymorphisms were not found to be significant risk factors for either TMDp or sleep-related oral behaviours. The association of waking-state oral behaviours with selected gene polymorphisms additionally supports previous assumptions that daytime bruxism is more closely linked to various stress manifestations, which might also be reflected through the variability related to the cellular antioxidative activity.

The frequency of selected polymorphisms, one in each gene coding for proteins with antioxidative properties (CAT, SOD2, GPX1, NQO1) was compared between patients suffering from pain-related temporomandibular disorders (TMDp;n=85) and control subjects (CTR;n=85). According to the Oral Behaviours Checklist score participants were divided into high-frequency parafunction (HFP;n=98) and low-frequency parafunction (LFP;n=72) groups. In addition, we have investigated the association of selected polymorphisms with participants' psychological (anxiety, depression) and psychosomatic (hypervigilance, somatosensory amplification) characteristics. Polymorphisms rs1001179, rs4880, rs1050450, rs689452 were genotyped using the genomic DNA extracted from buccal mucosa swabs and real-time TaqMan genotyping assays. No differences in genotype distribution between TMDp patients and control subjects were found. Still, TMDp patients who were homozygous for minor allele A, related to the GPX1 polymorphism rs1050450 reported significantly more waking-state oral behaviours compared to GA+GG genotype carriers (score: 30 vs. 23, p=0.019). Frequency of genotype AA for rs1050450 polymorphism was higher in HFP compared to LFP participants (14.3% vs. 4.2%, p =0.030). Most important predictors of waking-state oral behaviours were depression, anxiety, AA genotype (rs1050450) and female sex. Explored genetic factors were not found to be significant risk factors for either TMDp or sleep-related oral behaviours. The association of waking-state oral behaviours with selected gene polymorphisms additionally supports previous assumptions that the daytime bruxism is more closely linked to various stress manifestations, which might also be reflected through the variability related to cellular antioxidative activity.