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DNA methylation changes in fibromyalgia suggest the role of the immune-inflammatory response and central sensitization

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Detalhes bibliográficos
Resumo:Fibromyalgia (FM) has been explained as a result of gene-environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the <i>GCSAML</i> region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to <i>GCSAML</i> survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; <i>GRM2</i> methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the <i>GRM2</i> region were significantly associated with FM risk. Our study encourages better exploration of <i>GCSAML</i> and <i>GRM2</i> functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain.
Autores principais:Gerra, Maria Carla
Outros Autores:Carnevali, Davide; Ossola, Paolo; González-Villar, Alberto J.; Pedersen, Inge Søkilde; Triñanes, Yolanda; Donnini, Claudia; Manfredini, Matteo; Arendt-Nielsen, Lars; Carrillo-de-la-Peña, Maria Teresa
Assunto:Fibromyalgia Epigenetics Blood Biomarkers DNA methylation Depression Immune system Pain management
Ano:2021
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:Fibromyalgia (FM) has been explained as a result of gene-environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the <i>GCSAML</i> region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to <i>GCSAML</i> survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; <i>GRM2</i> methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the <i>GRM2</i> region were significantly associated with FM risk. Our study encourages better exploration of <i>GCSAML</i> and <i>GRM2</i> functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain.