The polymorphism Val158Met in the COMT gene: disrupted dopamine system in fibromyalgia patients?

The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene (COMT) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial re...

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Detalles Bibliográficos
Autores: Gerra, María Carla, Dallabona, Cristina, Manfredini, Matteo, Giordano, Rocco, Capriotti, Camilla, González Villar, Alberto Jacobo, Triñanes Pego, Yolanda, Arendt Nielsen, Lars, Carrillo de la Peña, María Teresa
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/45467
Acceso en línea:https://hdl.handle.net/10347/45467
Access Level:acceso abierto
Palabra clave:Val158Met
Fibromyalgia
COMT
Dopamine
Pain intensity
Fibromyalgia comorbidities
Descripción
Sumario:The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene (COMT) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial results on its role in fibromyalgia (FM). Here, the SNP Val158Met was analyzed in 294 FM patients (without comorbidities) and 209 healthy controls (without chronic pain). The concurrent impact of Val158Met genotypes and FM comorbid disorders (depression and sleep impairment) on FM risk were tested. In addition, the genotypic distribution of FM patients in relation to pain intensity was evaluated. The G allele (Val) resulted in being more represented in the FM group (57.8%) compared with the control group (48.8%; P = 0.037). Logistic regression highlighted that having the G/G (Val/Val) homozygous genotype was associated with 2 times higher risk of having FM compared with the A/A (Met/Met) carriers (P = 0.038), whereas depression and sleep impairment increased FM risk by 12 and 8 times, respectively (P < 0.001). However, considering only the FM patient group, the A/A homozygous genotype was significantly associated with severe pain intensity (P = 0.007). This study highlighted associations between the SNP Val158Met and both FM and pain intensity, suggesting a link between dopaminergic dysfunction and vulnerability to chronic pain. Further studies should explore this SNP in FM patients in conjunction with COMT enzymatic activity and other symptoms connected with the dopaminergic system such as depression or sleep impairment