Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers

Abstract

Fibromyalgia is a disease characterized by chronic widespread pain with additional symptoms, such as joint stiffness, fatigue, sleep disturbance, cognitive dysfunction, and depression. Currently, fibromyalgia diagnosis is based exclusively on a comprehensive clinical assessment, according to 2016 ACR criteria, but validated biological biomarkers associated with fibromyalgia have not yet been identified. Genome-wide association studies investigated genes potentially involved in fibromyalgia pathogenesis highlighting that genetic factors are possibly responsible for up to 50% of the disease susceptibility. Potential candidate genes found associated to fibromyalgia are SLC64A4, TRPV2, MYT1L, and NRXN3. Furthermore, a gene-environmental interaction has been proposed as triggering mechanism, through epigenetic alterations: In particular, fibromyalgia appears to be characterized by a hypomethylated DNA pattern, in genes implicated in stress response, DNA repair, autonomic system response, and subcortical neuronal abnormalities. Differences in the genome-wide expression profile of microRNAs were found among multiple tissues, indicating the involvement of distinct processes in fibromyalgia pathogenesis. Further studies should be dedicated to strength these preliminary findings, in larger multicenter cohorts, to identify reliable directions for biomarker research and clinical practice.

5ʹUTR polymorphism in the serotonergic receptor HTR3A gene is differently associated with striatal Dopamine D2/D3 receptor availability in the right putamen in Fibromyalgia patients and healthy controls—Preliminary evidence

“…The mechanism underlying the contrasting effects of SNP rs1062613 on baseline DRD2 binding in FMS patients compared to healthy controls remains unclear but conceivably may reflect interactions between this SNP and other genetic or environmental factors associated with FMS as there is a precedent for this kind of gene × diagnosis interaction in the literature (D'Agnelli et al, ). Based on the finding of an inverse association between DRD2 receptor availability and pain threshold in the right putamen in healthy subjects (Pertovaara et al, ), we expected a modulatory role of this SNP on pain processing via DRD2 receptor transmission.…”

Clinical Pharmacists in Chronic Care

“…Work disability was found to be 35% in US and Australia and 30% reported in Canada due to FM [266]. FM is more common in female compared to male, with a ratio of 2:1 [267] or 3:1 [268], although other studies reveal 85%-90% FM patients are middle aged women [269,270]. 30-50% of FM patients have anxiety and/or depression at the time of investigation [271], while patients have a lifetime history of depression (50-75%) [272] and depressive disorders (13%-63.8%) [273].…”

Biomarkers in temporomandibular disorder and trigeminal neuralgia: A conceptual framework for understanding chronic pain

“…Potential candidate genes identified include SLC64A4, TRPV2, MYT1L, and NRXN3. 39 Environmental factors and early life experiences may also modulate genome function through epigenetic mechanisms. Epigenetic changes in women with fibromyalgia have been identified using genome-wide methylation pattern analysis.…”