The results obtained from a recent study showed a lower percentage of Mu-positive B cells in subjects with FM than in controls. analysis of genetic, epigenetic and serological biomarkers. Symptoms often begin after physical or emotional trauma, but in many cases, there appears to be no obvious trigger. Women are more prone to developing the disease than men. Unfortunately, the conventional medical therapies that target this pathology produce limited benefits. They remain largely pharmacological in nature and tend to treat the symptomatic aspects of various disorders reported by the patient. The statistics, however, highlight the fact that 90% of people with fibromyalgia also turn to complementary medicine to manage their symptoms. is characterized by a single nucleotide polymorphism and is associated with chronic pain conditions (for example, mandibular joint disorder), as well as increased levels of depression and psychological disorders related to an alteration in serotonin reuptake [122]. The gene is expressed in mechano- and thermo-responsive neurons in the dorsal root and trigeminal ganglia and appears to be responsible for reducing the pain threshold in FM patients [123]. Other genetic polymorphisms that have been identified and associated with FM susceptibility are in the CPI-1205 serotonin transporter (5-HTT), catechol-O-methyltransferase (COMT) and serotonin 2A (5-HT2A) genes. However, subsequent meta-analyses could only confirm that the 102T/C polymorphism in the 5-HT2A receptor is connected with FM [124]. Therefore, further studies are needed to understand the role of these genes in chronic pain conditions such as FM. A genome-wide association and copy number variant study in 952 FM cases and 644 controls revealed the existence of two variables associated with FM. One variable is the single nucleotide polymorphism in a gene similar to myelin transcription factor 1 (MYT1L), which is responsible for neuronal differentiation and involved in cognitive alterations. The second is an intron copy number variable in the neurexin 3 (gene, which mediates the availability of dopamine, whose reduction can increase the sensitivity to pain typical of FM [126]. Another widely studied gene is and are possible candidate genes found to be related to fibromyalgia. Rabbit polyclonal to IL1R2 The frequency of polymorphisms in selected metabolism genes such as CYP P450 in FM pathology was also reported in another study [218]. In addition, a geneCenvironment association involving epigenetic changes was suggested as a triggering mechanism: fibromyalgia appears to be particularly characterized by a hypomethylated DNA pattern in genes involved in the stress response, DNA repair, the autonomic system response and subcortical neuronal abnormalities. In multiple tissues, differences were observed in the genome-wide expression profile of microRNAs, suggesting the involvement of various processes in the pathogenesis of fibromyalgia. Single nucleotide polymorphisms (SNPs) have been identified as possible candidates that are directly linked to FM susceptibility. 4.2. Epigenetic Modifications Previous studies have shown that early life experience and environmental factors in general may modulate genome function and the phenotype through epigenetic mechanisms without changing the DNA CPI-1205 sequence [231]. In chronic pain, epigenetic pathways have been shown to play a significant role in mediating long-term changes in the central and peripheral nervous systems [232]. In particular, changes in the state of methylation, histone modifications and the expression of miRNAs seem to arise in the presence of peripheral inflammation and nerve damage in pain-related regions [233,234]. As a valuable diagnostic method, epigenetic modifications (such as DNA methylation) should be further CPI-1205 investigated. The and genes were mapped to differently methylated sites, indicating the potential involvement of FM nervous system development, skeletal/organ system development and chromatin compaction pathways. Differentially methylated sites that correlated with the FM map were frequently identified in genes involved in biological functions such as DNA repair, immune response and membrane transport genes. 4.3. MicroRNAs as Novel Possible Biomarkers At least 30 percent of human genes are regulated by microRNAs [235], each of which can repress hundreds of genes [236]. The existence of microRNAs in various cellular compartments and their stability in the extracellular environment make them promising biomarkers to better understand the etiology.