The research hypothesis suggesting that DRD3 (rs6280) and 5-HTR2A (rs6313) polymorphisms play a significant role in the pathogenesis of bruxism has been accepted. Additionally, the mRNA expression of 5-HTR2A and DRD3 has been implicated in the genesis of bruxism. Analyzing gene expression in blood or the assessment of RNA within blood cells serves as a valuable strategy for identifying biomarkers and investigating the underlying mechanisms of various diseases, akin to Bruxism (15).Research indicates that approximately in 80% of the cases, blood cells exhibit a transcriptome similar to that of the brain (16).For instance, Sullivan et al. discovered significant overlap in gene expression related to neurotransmitter receptors between blood cells and various brain tissue (17).
In this study, we have found a significant association between bruxism and the 5-HTR2A gene rs6313 polymorphism. These results are consistent with those of Abe et al. (2012), who reported that the CC (polymorphic) genotype of the SNP rs6313 of the 5-HT2A receptor gene (102C > T) was positively associated with the etiology of sleep bruxism in the Japanese population (p = 0.001). The C allele was considered a risk factor for sleep bruxism (OR = 4.250, p = 0.004) (18).
Also, Cruz-Fierro et al. (2018) conducted a study aiming to determine the association between self-reported bruxism in the Mexican population, anxiety, and personal neuroticism with the SNP rs6313 polymorphism in the HTR2A receptor gene. They found a significant association between the C allele carrying the SNP rs6313 (102C > T) of the HTR2A gene and an increased risk of sleep bruxism (OR = 4.250; 95% CI 1,599 − 11,297; p = 0.004) (19).
In the study of Wieckiewicz et al. (2020), various SNPs were analyzed, indicating that the T allele of the HTR2A receptor gene rs6313 (p = 0.07) may be involved in sleep bruxism (20).
The results of our study showed an association between bruxism and increased HTR2A mRNA expression. It is important to recognize the role of serotonin signaling in the central nervous system. Serotonin, acting through its receptors including HTR2A, modulates various aspects of behavior and mood regulation (21).
The prefrontal cortex and hippocampal regions, where HTR2A is abundantly expressed, are crucial for emotional processing and motor control (22).
The disruption of serotonin signaling, as evidenced by altered HTR2A expression, may lead to aberrant neural activity and contribute to the manifestation of bruxism.
The study's finding of increased HTR2A mRNA expression in association with bruxism aligns with existing knowledge about the involvement of serotonin receptors in motor control and nociception. Dysregulation of serotonin receptors, including HTR2A, has been implicated in various neurological conditions such as depression, stress, anxiety disorders, and medication-induced bruxism (23).
This may support the effect of HTR2A mRNA expression on the genesis of bruxism, but further expression studies are needed to confirm this.
Concerning the DRD3 rs6280 polymorphism, the distribution of various genotypes among individuals with bruxism showed no statistically significant differences between the control and case groups. However, our findings suggest that the presence of the C allele is associated with a higher susceptibility to developing sleep bruxism. Sleep bruxism is considered a distinct entity due to putative differences in its etiology and phenotypic variance (24).
These findings align with those reported by Oporto et al. (2017), who found a significant association between the C allele of the DRD3 SNP receptor gene rs6280 and an increased risk of sleep bruxism (p = 0.02) (14).
In our study, we found an association between bruxism and reduced DRD3 mRNA expression.
The dysregulation of DRD3 mRNA expression has been implicated in several neuropsychiatric disorders, including Parkinson’s disease, addiction, bipolar disorder, and depression (25, 26).
However, no studies have evaluated the mRNA expression of DRD3 in bruxism.
Despite these compelling findings, the lack of consensus in bruxism etiology underscores the need for further clinical trials. Prospective studies with larger sample sizes, polysomnographic diagnosis, and diverse ethnicities are essential to confirm the involvement of serotonin and dopamine receptor gene polymorphisms in bruxism etiology. These genetic markers could potentially serve as crucial biomarkers for patient stratification, offering personalized approaches to diagnosis and treatment. The broader exploration of serotonin pathways in future investigations holds promise for advancing our understanding and improving therapeutic strategies for bruxism. Another limitation was that mRNA expression was only measured at one-time point, so longitudinal changes and their associations with clinical features remain unknown.