ORAL HEALTH EVIDENCE-BASED PRACTICE PROGRAM
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Title Specific Genetic Polymorphisms Are Associated with Either Increasing or Decreasing the Risk of Developing Temporomandibular Joint Disorders
Clinical Question In individuals with temporomandibular joint disorders, do genetics play a role in the severity of the disorder compared to individuals without a genetic predisposition?
Clinical Bottom Line For patients with temporomandibular joint disorders, certain genetic polymorphisms have been associated with increasing or decreasing the likelihood of developing the disorder. With new evidence supported by a systematic review showing that genetics is linked to developing TMD, there will be an opportunity to identify patients at a higher risk and to intervene with potential new drugs targeted at the genes that pose a risk.
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 26740320Melis/201626 articlesSystematic review of randomized trials
Key resultsThe role of genetic factors in the etiology of TMD was initially published in 1980. These early studies attempted to identify TMD severity amongst monozygotic and dizygotic twins and found no genetic predisposition to be evident. Also, studies confirmed that there was no correlation for TMD or other myofascial pain among first relatives. Eventually, several authors identified several different genetic polymorphic variants that contributed to a higher or lower risk of developing TMD. The specific polymorphisms of genes associated with developing TMD and its severity are listed here: serotonin activity and metabolism, T-cell receptor pathway, catecholamine activity and metabolism, estrogen activity, folate metabolism, glutathione activity, ANKH gene, major histocompatibility complex, extracellular matrix metabolism, cytokines activity and metabolism.
#2) 22074755Smith/20111,960 men and women aged 18-44 (348 TMD cases and 1,612 controls)Case-Control/Cohort Study
Key resultsA 7-year prospective cohort study involving a group of internationally recognized scientists assessed genetic factors that can initiate and precipitate factors for disorders of the temporomandibular joint. In total, there were seven genes related to TMD. Not all of the genetic polymorphisms were related to an increased risk of developing TMD, such as the NR3C1 glucocorticoid receptor that lowers the risk of TMD. However, polymorphisms of four other genes were correlated with an increased risk and severity of TMD. These polymorphisms involve the muscarinic cholinergic receptor 2 gene, the calcium/calmodulin-dependent protein kinase 4 gene, the interferon-related developmental regulator 1 gene, and protein-coupled receptor kinase 5 gene. A patient population of 1,960 was evaluated in this study. However, there was no correlation linked between genetic polymorphisms and the development of TMD to be found in the patient group. This implies that certain environmental, behavioral, and biological factors contribute more to the severity of TMD than genetics.
Evidence Search ("genetic therapy"[MeSH Terms] OR ("genetic"[All Fields] AND "therapy"[All Fields]) OR "genetic therapy"[All Fields] OR "genetic"[All Fields]) AND factors[All Fields] AND ("etiology"[Subheading] OR "etiology"[All Fields] OR "causality"[MeSH Terms] OR "causality"[All Fields]) AND temporomandibular[All Fields]
Comments on
The Evidence
Validity: The systematic review limited their search to humans and the English language. Also, PubMed was the only database used. Keywords specific to temporomandibular joint disorders and genetics were primarily included in the search. A total of 1,999 articles were found, but only 26 articles were selected. It is unknown if the authors considered the quality or risk for bias in each of the 26 articles. The authors declared no conflicts of interest. In the cohort/case-control study, there were limitations to the study. There was a big discrepancy between the numbers of cases vs. the number of controls. To enhance statistical power, the UNC cohort was included in the analysis. A total of 348 TMD cases and 1,612 controls were included. Also, heterogeneity likely impeded the ability to analyze subtle genetic defects. Perspective: I believe that the recent discovery of genetic polymorphisms related to TMD is a great advancement in the field of orofacial pain. Due to TMD being a multifactorial disorder, genetics are a new etiological factor to consider in patients where other contributing factors have been ruled out. Developing specific drugs targeted towards the genes posing a higher risk could eventually help lower the risk for individuals more predisposed to TMD, and it would also help to reduce the severity of the disorder.
Applicability Due to TMD being common among the general population and recent discoveries that genetic polymorphisms that may increase an individual’s risk, this is highly applicable information to dental practice. Discovering a new treatment approach may be beneficial to those affected by the disorder. Developing new drugs targeted at specific genes may eliminate the higher risk associated with TMD certain individuals face. However, the cost of genetic testing and new pharmaceuticals directed towards this disorder could potentially be a limiting factor.
Specialty/Discipline (General Dentistry) (Oral Surgery)
Keywords Temporomandibular joint disorders, etiology, genetics, gene polymorphism, genetic predisposition
ID# 3183
Date of submission: 04/26/2017spacer
E-mail hortoncs@livemail.uthscsa.edu
Author Chaz Horton
Co-author(s)
Co-author(s) e-mail
Faculty mentor/Co-author Edward Wright, DDS, MS
Faculty mentor/Co-author e-mail WrightE2@uthscsa.edu
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