[en] 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.
Disciplines :
Neurosciences & comportement
Auteur, co-auteur :
Berg, Fabian
Moser, Dirk A.
Hagena, Verena
Streit, Fabian
Mosch, Benjamin
KUMSTA, Robert ; University of Luxembourg > Faculty of Humanities, Education and Social Sciences (FHSE) > Department of Behavioural and Cognitive Sciences (DBCS)
Herpertz, Stephan
Diers, Martin
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
MicroRNA-Related Polymorphism and Their Association with Fibromyalgia.
Date de publication/diffusion :
2023
Titre du périodique :
Genes
ISSN :
2073-4425
Maison d'édition :
Multidisciplinary Digital Publishing Institute (MDPI), Suisse
Wolfe F. Clauw D.J. Fitzcharles M.A. Goldenberg D.L. Katz R.S. Mease P. Russell A.S. Russell I.J. Winfield J.B. Yunus M.B. The american college of rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity Arthritis Care Res. 2010 62 600 610 10.1002/acr.20140 20461783
Diers M. Neuroimaging the pain network—Implications for treatment Best Pract. Res. Clin. Rheumatol. 2019 33 101418 10.1016/j.berh.2019.05.003 31703795
Hauser W. Zimmer C. Felde E. Kollner V. What are the key symptoms of fibromyalgia? Schmerz 2008 22 176 183 18210165
Diers M. Koeppe C. Yilmaz P. Thieme K. Markela-Lerenc J. Schiltenwolf M. van Ackern K. Flor H. Pain ratings and somatosensory evoked responses to repetitive intramuscular and intracutaneous stimulation in fibromyalgia syndrome J. Clin. Neurophysiol. 2008 25 153 160 10.1097/WNP.0b013e31817759c5 18469725
Diers M. Schley M.T. Rance M. Yilmaz P. Lauer L. Rukwied R. Schmelz M. Flor H. Differential central pain processing following repetitive intramuscular proton/prostaglandin e-2 injections in female fibromyalgia patients and healthy controls Eur. J. Pain. 2011 15 716 723 10.1016/j.ejpain.2010.12.002
Gracely R.H. Petzke F. Wolf J.M. Clauw D.J. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia Arthritis Rheumatol. 2002 46 1333 1343 10.1002/art.10225
Mosch B. Hagena V. Herpertz S. Ruttorf M. Diers M. Neural correlates of control over pain in fibromyalgia patients NeuroImage Clin. 2023 37 103355 10.1016/j.nicl.2023.103355
Ablin J.N. Buskila D. Update on the genetics of the fibromyalgia syndrome Best Pract. Res. Clin. Rheumatol. 2015 29 20 28 10.1016/j.berh.2015.04.018
Ablin J.N. Cohen H. Buskila D. Mechanisms of disease: Genetics of fibromyalgia Nat. Clin. Pract. Rheum. 2006 2 671 678 10.1038/ncprheum0349
Buskila D. Sarzi-Puttini P. Ablin J.N. The genetics of fibromyalgia syndrome Pharmacogenomics 2007 8 67 74 10.2217/14622416.8.1.67
Galvez-Sanchez C.M. Duschek S. Reyes Del Paso G.A. Psychological impact of fibromyalgia: Current perspectives Psychol. Res. Behav. Manag. 2019 12 117 127 10.2147/PRBM.S178240 30858740
Walker E.A. Keegan D. Gardner G. Sullivan M. Bernstein D. Katon W.J. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: II. Sexual, physical, and emotional abuse and neglect Psychosom. Med. 1997 59 572 577 10.1097/00006842-199711000-00003 9407574
Walker E.A. Keegan D. Gardner G. Sullivan M. Katon W.J. Bernstein D. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: I. Psychiatric diagnoses and functional disability Psychosom. Med. 1997 59 565 571 10.1097/00006842-199711000-00002 9407573
Lee R.C. Feinbaum R.L. Ambros V. The C. elegans heterochronic gene lin-4 encodes small rnas with antisense complementarity to lin-14 Cell 1993 75 843 854 10.1016/0092-8674(93)90529-Y
Hammond S.M. An overview of micrornas Adv. Drug. Deliv. Rev. 2015 87 3 14 10.1016/j.addr.2015.05.001
Saunders M.A. Liang H. Li W.H. Human polymorphism at micrornas and microrna target sites Proc. Natl. Acad. Sci. USA 2007 104 3300 3305 10.1073/pnas.0611347104
Brum C.B. Paixao-Cortes V.R. Carvalho A.M. Martins-Silva T. Carpena M.X. Ulguim K.F. Luquez K.Y.S. Salatino-Oliveira A. Tovo-Rodrigues L. Genetic variants in mirnas differentially expressed during brain development and their relevance to psychiatric disorders susceptibility World J. Biol. Psychiatry 2021 22 456 467 10.1080/15622975.2020.1834618
Miller B.H. Wahlestedt C. Microrna dysregulation in psychiatric disease Brain Res. 2010 1338 89 99 10.1016/j.brainres.2010.03.035
Cammaerts S. Strazisar M. De Rijk P. Del Favero J. Genetic variants in microrna genes: Impact on microrna expression, function, and disease Front. Genet. 2015 6 186 10.3389/fgene.2015.00186
Caputo V. Sinibaldi L. Fiorentino A. Parisi C. Catalanotto C. Pasini A. Cogoni C. Pizzuti A. Brain derived neurotrophic factor (bdnf) expression is regulated by micrornas mir-26a and mir-26b allele-specific binding PLoS ONE 2011 6 e28656 10.1371/journal.pone.0028656
Gong Y. Wu C.N. Xu J. Feng G. Xing Q.H. Fu W. Li C. He L. Zhao X.Z. Polymorphisms in microrna target sites influence susceptibility to schizophrenia by altering the binding of mirnas to their targets Eur. Neuropsychopharmacol. 2013 23 1182 1189 10.1016/j.euroneuro.2012.12.002
Rykova E. Ershov N. Damarov I. Merkulova T. Snps in 3’utr mirna target sequences associated with individual drug susceptibility Int. J. Mol. Sci. 2022 23 13725 10.3390/ijms232213725
Dutta D. Brummett C.M. Moser S.E. Fritsche L.G. Tsodikov A. Lee S. Clauw D.J. Scott L.J. Heritability of the fibromyalgia phenotype varies by age Arthritis Rheumatol. 2020 72 815 823 10.1002/art.41171
Bjersing J.L. Lundborg C. Bokarewa M.I. Mannerkorpi K. Profile of cerebrospinal micrornas in fibromyalgia PLoS ONE 2013 8 e78762 10.1371/journal.pone.0078762 24205312
Bjersing J.L. Bokarewa M.I. Mannerkorpi K. Profile of circulating micrornas in fibromyalgia and their relation to symptom severity: An exploratory study Rheumatol. Int. 2015 35 635 642 10.1007/s00296-014-3139-3
Cerda-Olmedo G. Mena-Duran A.V. Monsalve V. Oltra E. Identification of a microrna signature for the diagnosis of fibromyalgia PLoS ONE 2015 10 e0121903
Masotti A. Baldassarre A. Guzzo M.P. Iannuccelli C. Barbato C. Di Franco M. Circulating microrna profiles as liquid biopsies for the characterization and diagnosis of fibromyalgia syndrome Mol. Neurobiol. 2017 54 7129 7136 10.1007/s12035-016-0235-2
Sakai A. Suzuki H. Microrna and pain Adv. Exp. Med. Biol. 2015 888 17 39 26663177
Wolfe F. Clauw D.J. Fitzcharles M.A. Goldenberg D.L. Hauser W. Katz R.L. Mease P.J. Russell A.S. Russell I.J. Walitt B. 2016 revisions to the 2010/2011 fibromyalgia diagnostic criteria Semin. Arthritis Rheum. 2016 46 319 329
Kerns R.D. Turk D.C. Rudy T.E. The west haven-yale multidimensional pain inventory (whympi) Pain 1985 23 345 356 10.1016/0304-3959(85)90004-1 4088697
Flor H. Rudy T.E. Birbaumer N. Streit B. Schugens M.M. The applicability of the west haven-yale multidimensional pain inventory in german-speaking countries. Data on the reliability and validity of the mpi-d Schmerz 1990 4 82 87 10.1007/BF02527839
Vonkorff M. Ormel J. Keefe F.J. Dworkin S.F. Grading the severity of chronic pain Pain 1992 50 133 149 10.1016/0304-3959(92)90154-4 1408309
Hauser W. Jung E. Erbsloh-Moller B. Gesmann M. Kuhn-Becker H. Petermann F. Langhorst J. Weiss T. Winkelmann A. Wolfe F. Validation of the fibromyalgia survey questionnaire within a cross-sectional survey PLoS ONE 2012 7 e37504 10.1371/journal.pone.0037504 22662163
Offenbaecher M. Waltz M. Schoeps P. Validation of a german version of the fibromyalgia impact questionnaire (fiq-g) J. Rheumatol. 2000 27 1984 1988
Flor H. Behle D.J. Birbaumer N. Assessment of pain-related cognitions in chronic pain patients Behav. Res. Ther. 1993 31 63 73 10.1016/0005-7967(93)90044-U 8417730
Radloff L.S. The ces-d scale: A self-report depression scale for research in the general population Appl. Psychol. Meas. 1977 1 385 401 10.1177/014662167700100306
Hautzinger M. Bailer M. Allgemeine Depressionsskala (ADS) Die Deutsche Version Des Ces—d. Beltz Test Beltz Weinheim, Germany 1993
Miller S.A. Dykes D.D. Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells Nucleic Acids Res. 1988 16 1215 10.1093/nar/16.3.1215
Purcell S. Neale B. Todd-Brown K. Thomas L. Ferreira M.A.R. Bender D. Maller J. Sklar P. de Bakker P.I.W. Daly M.J. et al. Plink: A tool set for whole-genome association and population-based linkage analyses Am. J. Hum. Genet. 2007 81 559 575 10.1086/519795
Wilkins O.M. Titus A.J. Gui J. Eliot M. Butler R.A. Sturgis E.M. Li G. Kelsey K.T. Christensen B.C. Genome-scale identification of microrna-related snps associated with risk of head and neck squamous cell carcinoma Carcinogenesis 2017 38 986 993 10.1093/carcin/bgx056
Liu C.J. Fu X. Xia M. Zhang Q. Gu Z. Guo A.Y. Mirnasnp-v3: A comprehensive database for snps and disease-related variations in mirnas and mirna targets Nucleic Acids Res. 2021 49 D1276 D1281 10.1093/nar/gkaa783
Gong J. Liu C. Liu W. Wu Y. Ma Z. Chen H. Guo A.Y. An update of mirnasnp database for better snp selection by gwas data, mirna expression and online tools Database 2015 2015 bav029 10.1093/database/bav029 25877638
Gong J. Tong Y. Zhang H.M. Wang K. Hu T. Shan G. Sun J. Guo A.Y. Genome-wide identification of snps in microrna genes and the snp effects on microrna target binding and biogenesis Hum. Mutat. 2012 33 254 263 10.1002/humu.21641 22045659
Chen Y.H. Wang X.W. Mirdb: An online database for prediction of functional microrna targets Nucleic Acids Res. 2020 48 D127 D131 10.1093/nar/gkz757 31504780
Liu W. Wang X. Prediction of functional microrna targets by integrative modeling of microrna binding and target expression data Genome. Biol. 2019 20 18 10.1186/s13059-019-1629-z
Arnold L.M. Fan J.B. Russell I.J. Yunus M.B. Khan M.A. Kushner I. Olson J.M. Iyengar S.K. The fibromyalgia family study: A genome-wide linkage scan study Arthritis Rheumatol. 2013 65 1122 1128 10.1002/art.37842
Docampo E. Escaramis G. Gratacos M. Villatoro S. Puig A. Kogevinas M. Collado A. Carbonell J. Rivera J. Vidal J. et al. Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system Pain 2014 155 1102 1109 10.1016/j.pain.2014.02.016
Johnston K.J.A. Adams M.J. Nicholl B.I. Ward J. Strawbridge R.J. Ferguson A. McIntosh A.M. Bailey M.E.S. Smith D.J. Genome-wide association study of multisite chronic pain in uk biobank PLoS Genet. 2019 15 e1008164 10.1371/journal.pgen.1008164
Rahman M.S. Winsvold B.S. Chavez Chavez S.O. Borte S. Tsepilov Y.A. Sharapov S.Z. Pain H.A.-I. Aulchenko Y.S. Hagen K. Fors E.A. et al. Genome-wide association study identifies rnf123 locus as associated with chronic widespread musculoskeletal pain Ann. Rheum. Dis. 2021 80 1227 1235 10.1136/annrheumdis-2020-219624
D’Agnelli S. Arendt-Nielsen L. Gerra M.C. Zatorri K. Boggiani L. Baciarello M. Bignami E. Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers Mol. Pain 2019 15 1744806918819944 10.1177/1744806918819944
Jin Y. Lee C.G. Single nucleotide polymorphisms associated with microrna regulation Biomolecules 2013 3 287 302 10.3390/biom3020287
Hummel E.M. Hessas E. Muller S. Beiter T. Fisch M. Eibl A. Wolf O.T. Giebel B. Platen P. Kumsta R. et al. Cell-free DNA release under psychosocial and physical stress conditions Transl. Psychiatry 2018 8 236 10.1038/s41398-018-0264-x 30374018
Moser D. Ekawardhani S. Kumsta R. Palmason H. Bock C. Athanassiadou Z. Lesch K.P. Meyer J. Functional analysis of a potassium-chloride co-transporter 3 (slc12a6) promoter polymorphism leading to an additional DNA methylation site Neuropsychopharmacology 2009 34 458 467 10.1038/npp.2008.77
Philippidou D. Schmitt M. Moser D. Margue C. Nazarov P.V. Muller A. Vallar L. Nashan D. Behrmann I. Kreis S. Signatures of micrornas and selected microrna target genes in human melanoma Cancer Res. 2010 70 4163 4173 10.1158/0008-5472.CAN-09-4512
Jurkiewicz M. Moser D. Koller A. Yu L. Chen E.I. Bennett D.A. Canli T. Integration of postmortem amygdala expression profiling, gwas, and functional cell culture assays: Neuroticism-associated synaptic vesicle glycoprotein 2a (sv2a) gene is regulated by mir-133a and mir-218 Transl. Psychiatry 2020 10 297 10.1038/s41398-020-00966-4
Jurkiewicz M.M. Mueller-Alcazar A. Moser D.A. Jayatilaka I. Mikhailik A. Ferri J. Fogelman N. Canli T. Integrated microrna and mrna gene expression in peripheral blood mononuclear cells in response to acute psychosocial stress: A repeated-measures within-subject pilot study BMC Res. Notes 2021 14 222 10.1186/s13104-021-05635-3 34082815
Beiter T. Niess A.M. Moser D. Transcriptional memory in skeletal muscle. Don’t forget (to) exercise J. Cell. Physiol. 2020 235 5476 5489 10.1002/jcp.29535 31967338
Ehlert T. Simon P. Moser D.A. Epigenetics in sports Sports Med. 2013 43 93 110 10.1007/s40279-012-0012-y
Hummel E. Elgizouli M. Sicorello M. Leitao E. Beygo J. Schroder C. Zeschnigk M. Muller S. Herpertz S. Moser D. et al. No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder Sci. Rep. 2022 12 17347 10.1038/s41598-022-22177-1
Hummel E.M. Piovesan K. Berg F. Herpertz S. Kessler H. Kumsta R. Moser D.A. Mitochondrial DNA as a marker for treatment-response in post-traumatic stress disorder Psychoneuroendocrinology 2023 148 105993 10.1016/j.psyneuen.2022.105993
Schwaiger M. Grinberg M. Moser D. Zang J.C. Heinrichs M. Hengstler J.G. Rahnenfuhrer J. Cole S. Kumsta R. Altered stress-induced regulation of genes in monocytes in adults with a history of childhood adversity Neuropsychopharmacology 2016 41 2530 2540 10.1038/npp.2016.57
Zang J.C.S. May C. Hellwig B. Moser D. Hengstler J.G. Cole S. Heinrichs M. Rahnenfuhrer J. Marcus K. Kumsta R. Proteome analysis of monocytes implicates altered mitochondrial biology in adults reporting adverse childhood experiences Transl. Psychiatry 2023 13 31 10.1038/s41398-023-02320-w 36720844
Clos-Garcia M. Andrés-Marin N. Fernández-Eulate G. Abecia L. Lavín J.L. van Liempd S. Cabrera D. Royo F. Valero A. Errazquin N. et al. Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia EBioMedicine 2019 46 499 511
Leinders M. Doppler K. Klein T. Deckart M. Rittner H. Sommer C. Üçeyler N. Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome Pain 2016 157 2493 2503
Braun A. Evdokimov D. Frank J. Sommer C. Üçeyler N. MiR103a-3p and miR107 are related to adaptive coping in a cluster of fibromyalgia patients PLoS ONE 2020 15 e0239286
Hussein M. Fathy W. Abdelaleem E.A. Nasser M. Yehia A. Elanwar R. The Impact of Micro RNA-320a Serum Level on Severity of Symptoms and Cerebral Processing of Pain in Patients with Fibromyalgia Pain Med. 2022 23 2061 2072
Nepotchatykh E. Caraus I. Elremaly W. Leveau C. Elbakry M. Godbout C. Rostami-Afshari B. Petre D. Khatami N. Franco A. et al. Circulating microRNA expression signatures accurately discriminate myalgic encephalomyelitis from fibromyalgia and comorbid conditions Sci. Rep. 2023 13 1896
Erbacher C. Vaknine S. Moshitzky G. Lobentanzer S. Eisenberg L. Evdokimov D. Sommer C. Greenberg D.S. Soreq H. Üçeyler N. Distinct CholinomiR Blood Cell Signature as a Potential Modulator of the Cholinergic System in Women with Fibromyalgia Syndrome Cells 2022 11 1276
