Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia

Abstract

Background Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM. Methods. A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β). Results. COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients. Discussion Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.

Genome-wide association study for single nucleotide polymorphism associated with mural and cumulus granulosa cells of PCOS (polycystic ovary syndrome) and non-PCOS patients

“…Placental, adrenal, and ovarian Catechol-O-methyltransferase (COMT) expression is first implicated in symptoms of PCOS such as fibromyalgia, chronic fatigue, and mild inflammation. As per the literature and results of present study these genes were also found in granulosa cells, which indicates that a significant role may be played by the genes of granulosa cells [85]. The PCOS-related behaviours of diabetic nephropathy, coronary artery disease, and inflammatory illness were all discovered in granulosa cells, indicating that HP may have a role in the aetiology of PCOS similar to the fact produced in earlier study they were found strongly associated with obesity and glucose tolerance [42].…”

DNA Methylation Patterns in Relation to Acute Severity and Duration of Anxiety and Depression

“…They also observed a complex and different relationship between COMT methylation and prefrontal white matter connectivity in both groups [ 54 ]. Polli and colleagues found no significant association between DNA methylation of the COMT gene and symptoms in patients with chronic fatigue syndrome and fibromyalgia [ 98 ]. In healthy subjects, higher stress levels and lower COMT methylation were reported to be associated with a decreased cortical efficiency [ 99 ].…”

The Biology of Stress Intolerance in Patients with Chronic Pain—State of the Art and Future Directions

“…Genetics and epigenetics are thus both associated with pain and stress. Moreover, genetic polymorphisms can influence DNA methylation in several genes [ 131 , 132 , 133 , 134 , 135 ], as is the case for COMT [ 136 , 137 ]. It is thus likely that both genetics and epigenetics underly the role of the ANS and HPA axis in stress intolerance in patients with chronic pain.…”