Distinct CholinomiR Blood Cell Signature as a Potential Modulator of the Cholinergic System in Women with Fibromyalgia Syndrome

Erbacher, Christoph; Vaknine, Shani; Moshitzky, Gilli; Lobentanzer, Sebastian; Eisenberg, Lina; Evdokimov, Dimitar; Sommer, Claudia; Greenberg, David; Soreq, Hermona; Üçeyler, Nurcan

doi:10.3390/cells11081276

Cited by 9 publications

(4 citation statements)

References 95 publications

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“…Fibromyalgia (FM) is a limiting chronic syndrome characterized by widespread musculoskeletal pain accompanied by a wide variety of related symptoms such as fatigue, sleep disturbances and other cognitive disturbances. FM prevalence is estimated to range from 2% to 4% ( 1 ), primarily affecting adult women from developed economies, although men may be underdiagnosed ( 2 ). Currently, diagnosis is mainly based on the criteria of the American College of Rheumatology (ACR), which include the presence of widespread pain affecting both sides of the body and occurring above and below the waist.…”

Section: Introductionmentioning

confidence: 99%

Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up

del Amo,

Durán-González,

Ramírez-Tejero

et al. 2023

Front. Neurol.

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Fibromyalgia (FM) is a complex disease that is characterized by chronic musculoskeletal pain and has great economic impact. FM prevalence is about 2% to 4% worldwide, affecting mainly middle-aged women, and its complex pathophysiology complicates diagnosis, treatment and the findings of solid biomarkers. Previous studies have suggested an association between the disease and oxidative stress, mitochondrial metabolism, intestinal microbiota and inflammation, providing sufficient data to support the multifactorial origin of FM. Hence, the objective of this randomized, prospective, low-interventional, double-blinded and placebo-controlled clinical trial is the development of a specific panel of FM biomarkers and the evaluation of their response to a six-month nutritional intervention based on the Mediterranean diet supplemented with extra virgin olive oil (EVOO). For this purpose, the experimental design implies the recruitment of a large cohort of female Spanish patients. Middle-aged women who meet the diagnostic criteria for FM according to the American College of Rheumatology (ACR) will be eligible, along with age-matched healthy women. Both groups will be randomly divided into placebo (olive oil, OO) and treatment groups (extra virgin olive oil, EVOO), and will provide samples at the beginning (T0), after 3 months of nutritional intervention (T1), at the end of the nutritional intervention in 6 months (T2), and 6 months after the end of nutritional intervention (TF), being enrolled for 1 year. Data will be collected through health questionnaires, and whole blood and stool samples will be taken and analyzed. Blood will be used for western-blotting and proteomic analysis of mitochondrial homeostasis and plasma proteome, while stool will undergo metagenomic analysis, respectively. This study represents the first low-interventional investigation with more than 200 participants focused on exploring the association of oxidative stress, mitochondrial metabolism, intestinal microbiota and related pathways with a nutritional intervention in the context of FM. As a result, the outcomes of this study will significantly contribute to the development of a comprehensive and robust panel of diagnostic biomarkers, and will shed some light on their modulation with non-pharmacological therapies such as nutrition.Clinical trial registration: https://clinicaltrials.gov/study/NCT05921409, identifier: NCT05921409.

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Section: Introductionmentioning

confidence: 99%

Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up

del Amo,

Durán-González,

Ramírez-Tejero

et al. 2023

Front. Neurol.

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“…Erbacher et al reported that micro-RNA-182-5p targets bone morphogenic protein receptor 2 (BMPR-2) and interleukin 6 (IL-6) in FM patients. This is evidenced by increased levels of micro-RNA-182-5p and decreased BMPR-2 and IL-6 [ 111 ]. Sommer et al reported that the micro-RNA-103a/107 family is correlated with pro-inflammation and pain severity [ 112 ].…”

Section: Epigenetic Contributions To the Development Of Fmmentioning

confidence: 99%

“…In contrast to the above, Surendran et al did not find any significant differences in serum IL-6 and IL-8 in an Indian FM population compared to healthy controls [ 125 ], suggesting that there is a heterogeneous cytokine profile in different FM ethnic groups. Additionally, Erbacher et al found that a miRNA targets IL-6 in FM individuals, resulting in decreased IL-6 production [ 111 ]. They postulated that the miRNA may have acted in a compensatory manner to confine an already pro-inflammatory state.…”

Section: Epigenetic Contributions To the Development Of Fmmentioning

confidence: 99%

A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia

et al. 2023

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This narrative review summarizes the current knowledge of the genetic and epigenetic contributions to the development of fibromyalgia (FM). Although there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the catecholaminergic pathway, the serotonergic pathway, pain processing, oxidative stress, and inflammation may influence susceptibility to FM and the severity of its symptoms. Furthermore, epigenetic changes at the DNA level may lead to the development of FM. Likewise, microRNAs may impact the expression of certain proteins that lead to the worsening of FM-associated symptoms.

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“…The following supporting information can be downloaded at: https://www. mdpi.com/article/10.3390/genes14071312/s1, Table S1: literature miRNAs [24][25][26][27][63][64][65][66][67][68]; Table S2: miRNASNP-v3 prediction; Table S3: miRDB target prediction.…”

Section: Supplementary Materialsmentioning

confidence: 99%

MicroRNA-Related Polymorphism and Their Association with Fibromyalgia

Berg

Moser

Hagena

et al. 2023

Genes

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MicroRNAs are tissue-specific expressed short RNAs that serve post-transcriptional gene regulation. A specific microRNA can bind to mRNAs of different genes and thereby suppress their protein production. In the context of the complex phenotype of fibromyalgia, we used the Axiom miRNA Target Site Genotyping Array to search genome-wide for DNA variations in microRNA genes, their regulatory regions, and in the 3’UTR of protein-coding genes. To identify disease-relevant DNA polymorphisms, a cohort of 176 female fibromyalgia patients was studied in comparison to a cohort of 162 healthy women. The association between 48,329 markers and fibromyalgia was investigated using logistic regression adjusted for population stratification. Results show that 29 markers had p-values < 1 × 10−3, and the strongest association was observed for rs758459 (p-value of 0.0001), located in the Neurogenin 1 gene which is targeted by hsa-miR-130a-3p. Furthermore, variant rs2295963 is predicted to affect binding of hsa-miR-1-3p. Both microRNAs were previously reported to be differentially expressed in fibromyalgia patients. Despite its limited statistical power, this study reports two microRNA-related polymorphisms which may play a functional role in the pathogenesis of fibromyalgia. For a better understanding of the disease pattern, further functional analyses on the biological significance of microRNAs and microRNA-related polymorphisms are required.

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Distinct CholinomiR Blood Cell Signature as a Potential Modulator of the Cholinergic System in Women with Fibromyalgia Syndrome

Cited by 9 publications

References 95 publications

Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up

Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up

A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia

MicroRNA-Related Polymorphism and Their Association with Fibromyalgia

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