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Condicionantes genómicas no tratamento da dor da disfunção temporomandibular
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Abstract(s)
A disfunção temporomandibular (DTM) é um distúrbio que afeta 5 a 12% da população, sendo que a dor é o principal sintoma que leva o indivíduo a procurar tratamento.
A dor é uma condição muito complexa e influenciada por diversos fatores, sendo
que os fatores genéticos e ambientais têm um papel importante na interindividualidade da dor, assim como na resposta à terapêutica.
Deste modo, com base na evidência científica, constatou-se que existem vários genes envolvidos na suscetibilidade de desenvolver dor persistente e DTM, entre eles: o
gene que codifica o recetor alfa-estrogénio (Erα), em que existem polimorfismos
associados a distúrbios dolorosos da articulação temporomandibular (ATM); o gene que
codifica a catecolamina-O-metiltransferase (COMT), em que a sua baixa atividade está
relacionada com estados de dor persistentes; o gene que codifica o transportador de
serotonina (5-HTT), em que existe um polimorfismo responsável por duas variantes
alélicas, a curta e a longa, em que a variante longa está associada a indivíduos com DTM e o gene que codifica o recetor beta adrenérgico 2 (ADRβ2), em que existem três
haplótipos (H1, H2 e H3), sendo que o haplótipo H1 demonstra ter um papel protetor na
suscetibilidade de desenvolver DTM.
Para além disso, existem mecanismos epigenéticos que podem amplificar ou silenciar a expressão dos genes. A metilação do DNA e a descetilação das histonas estão relacionados com a repressão génica, enquanto a acetilação das histonas promove o
aumento da expressão génica.
Assim, através da compreensão das variantes genéticas responsáveis pela DTM e
estados de dor persistente, bem como os mecanismos epigenéticos envolvidos, a
terapêutica epigenética parece ter um futuro promissor no tratamento da dor.
Temporomandibular dysfunction (TMD) is a disorder that affects 5 to 12% of the population, and pain is the main symptom that leads the individual to seek treatment. Pain is a very complex condition influenced by several factors, and genetic and environmental factors play an important role in pain interindividuality, as well as in response to therapy. Thus, based on scientific evidence, it has been found that there are several genes involved in the susceptibility to developing persistent pain and TMD, including: the gene encoding the alpha-estrogen receptor (Erα), in which there are polymorphisms associated with painful temporomandibular joint disorders; the gene encoding catecholamine-Omethyltransferase (COMT), where its low activity is related to persistent states of pain; the gene encoding the serotonin transporter (5-HTT), in which there is a polymorphism responsible for two allelic variants, the short and the long, where the long variant is associated with individuals with TMD, and the gene that encodes the beta-2 adrenergic receptor (ADRβ2), in which there are three haplotypes (H1, H2 and H3), and the H1 haplotype has a protective role in the susceptibility of developing TMD. In addition, there are epigenetic mechanisms that can amplify or silence gene expression. DNA methylation and histone deacetylation are related to gene repression, whereas histone acetylation promotes increased gene expression. Thus, by understanding the genetic variants responsible for TMD and persistent pain states, as well as the epigenetic mechanisms involved, epigenetic therapy appears to have a promising future in pain management.
Temporomandibular dysfunction (TMD) is a disorder that affects 5 to 12% of the population, and pain is the main symptom that leads the individual to seek treatment. Pain is a very complex condition influenced by several factors, and genetic and environmental factors play an important role in pain interindividuality, as well as in response to therapy. Thus, based on scientific evidence, it has been found that there are several genes involved in the susceptibility to developing persistent pain and TMD, including: the gene encoding the alpha-estrogen receptor (Erα), in which there are polymorphisms associated with painful temporomandibular joint disorders; the gene encoding catecholamine-Omethyltransferase (COMT), where its low activity is related to persistent states of pain; the gene encoding the serotonin transporter (5-HTT), in which there is a polymorphism responsible for two allelic variants, the short and the long, where the long variant is associated with individuals with TMD, and the gene that encodes the beta-2 adrenergic receptor (ADRβ2), in which there are three haplotypes (H1, H2 and H3), and the H1 haplotype has a protective role in the susceptibility of developing TMD. In addition, there are epigenetic mechanisms that can amplify or silence gene expression. DNA methylation and histone deacetylation are related to gene repression, whereas histone acetylation promotes increased gene expression. Thus, by understanding the genetic variants responsible for TMD and persistent pain states, as well as the epigenetic mechanisms involved, epigenetic therapy appears to have a promising future in pain management.
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz
Keywords
Disfunção temporomandibular Dor Genética Epigenética