Skip to main content
SpringerLink
Log in

Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with susceptibility to fibromyalgia and fibromyalgia impact questionnaire (FIQ) score in fibromyalgia patients. We conducted a meta-analysis of the associations of the COMT Val158Met polymorphism with fibromyalgia risk as well as FIQ score in fibromyalgia patients. A total of 993 fibromyalgia patients and 778 controls from 10 studies on the COMT Val158Met polymorphism and 538 fibromyalgia patients from 5 studies on the COMT Val158Met polymorphism and FIQ score were included in this meta-analysis. The meta-analysis revealed an association between fibromyalgia and the COMT Met/Met + Val/Met genotype in all study subjects (odds ratio (OR) 1.635, 95 % confidence interval (CI) 1.029–2.597, p = 0.037). However, stratification by ethnicity indicated no association between the Met/Met + Val/Met genotype and fibromyalgia in the European and Turkish populations (OR 1.202, 95 % CI 0.876–1.649, p = 0.255; OR 2.132, 95 % CI 0.764–5.949, p = 0.148, respectively). Analysis using other genetic models showed no association between the COMT Val158Met polymorphism and fibromyalgia. The meta-analysis also revealed that the FIQ score was significantly higher in individuals with the COMT Met/Met genotype than in those with the Val/Val genotype [weighted mean difference (WMD) = 14.39, 95 % CI 3.316–25.48, p = 0.011] and the Val/Met genotype (WMD = 5.108, 95 % CI 2.212–4.891, p = 0.021). This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Neumann L, Buskila D (2003) Epidemiology of fibromyalgia. Curr Pain Headache Rep 7(5):362–368

    Article  PubMed  Google Scholar 

  2. Wallace DJ, Linker-Israeli M, Hallegua D, Silverman S, Silver D, Weisman MH (2001) Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology 40(7):743–749

    Article  CAS  PubMed  Google Scholar 

  3. Buskila D, Sarzi-Puttini P (2006) Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome. Arthritis Res Ther 8(5):218

    Article  PubMed Central  PubMed  Google Scholar 

  4. Lee YH, Choi SJ, Ji JD, Song GG (2012) Candidate gene studies of fibromyalgia: a systematic review and meta-analysis. Rheumatol Int 32(2):417–426

  5. Kaenmaki M, Tammimaki A, Myohanen T, Pakarinen K, Amberg C, Karayiorgou M et al (2010) Quantitative role of COMT in dopamine clearance in the prefrontal cortex of freely moving mice. J Neurochem 114(6):1745–1755

    Article  CAS  PubMed  Google Scholar 

  6. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM (1996) Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6(3):243–250

    Article  CAS  PubMed  Google Scholar 

  7. Martinez-Jauand M, Sitges C, Rodriguez V, Picornell A, Ramon M, Buskila D et al (2013) Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene. Eur J Pain 17(1):16–27

    Article  CAS  PubMed  Google Scholar 

  8. Desmeules J, Piguet V, Besson M, Chabert J, Rapiti E, Rebsamen M et al (2012) Psychological distress in fibromyalgia patients: a role for catechol-O-methyl-transferase Val158met polymorphism. Health Psychol 31(2):242–249

    Article  PubMed  Google Scholar 

  9. Matsuda JB, Barbosa FR, Morel LJ, de Castro Franca S, Zingaretti SM, da Silva LM et al (2010) Serotonin receptor (5-HT 2A) and catechol-O-methyltransferase (COMT) gene polymorphisms: triggers of fibromyalgia? Rev Bras Reumatol 50(2):141–149

    Article  PubMed  Google Scholar 

  10. Cohen H, Neumann L, Glazer Y, Ebstein RP, Buskila D (2009) The relationship between a common catechol-O-methyltransferase (COMT) polymorphism val(158) met and fibromyalgia. Clin Exp Rheumatol 27(5 Suppl 56):S51–S56

    CAS  PubMed  Google Scholar 

  11. Potvin S, Larouche A, Normand E, de Souza JB, Gaumond I, Grignon S et al (2009) DRD3 Ser9Gly polymorphism is related to thermal pain perception and modulation in chronic widespread pain patients and healthy controls. J Pain 10(9):969–975

    Article  CAS  PubMed  Google Scholar 

  12. Tander B, Gunes S, Boke O, Alayli G, Kara N, Bagci H et al (2008) Polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase genes: a study on fibromyalgia susceptibility. Rheumatol Int 28(7):685–691

    Article  CAS  PubMed  Google Scholar 

  13. Vargas-Alarcon G, Fragoso JM, Cruz-Robles D, Vargas A, Vargas A, Lao-Villadoniga JI et al (2007) Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis Res Ther 9(5):R110

    Article  PubMed Central  PubMed  Google Scholar 

  14. Gursoy S, Erdal E, Herken H, Madenci E, Alasehirli B, Erdal N (2003) Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int 23(3):104–107

    PubMed  Google Scholar 

  15. Fernandez-de-las-Penas C, Penacoba-Puente C, Cigaran-Mendez M, Diaz-Rodriguez L, Rubio-Ruiz B, Arroyo-Morales M (2014) Has catechol-O-methyltransferase genotype (Val158Met) an influence on endocrine, sympathetic nervous and humoral immune systems in women with fibromyalgia syndrome? Clin J Pain 30(3):199–204

    Article  PubMed  Google Scholar 

  16. Barbosa FR, Matsuda JB, Mazucato M, de Castro Franca S, Zingaretti SM, da Silva LM et al (2012) Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients. Rheumatol Int 32(2):427–430

    Article  CAS  PubMed  Google Scholar 

  17. Finan PH, Zautra AJ, Davis MC, Lemery-Chalfant K, Covault J, Tennen H (2011) COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia. Pain 152(2):300–307

    Article  PubMed Central  PubMed  Google Scholar 

  18. Garcia-Fructuoso FJ, Lao-Villadoniga JI, Beyer K, Santos C (2006) Relationship between COMT gene genotypes and severity of fibromyalgia. Reumatol Clin 2(4):168–172

    Article  Google Scholar 

  19. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27(9):827–833

    Article  CAS  PubMed  Google Scholar 

  20. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2010) Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep 37(1):227–234

  21. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38(6):3643–3651

    Article  CAS  PubMed  Google Scholar 

  22. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  23. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  24. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29(3):306–309

    Article  CAS  PubMed  Google Scholar 

  26. Tammimaki A, Mannisto PT (2012) Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis. Pharmacogenet Genomics 22(9):673–691

    Article  PubMed  Google Scholar 

  27. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE et al (2001) Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 98(12):6917–6922

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W (2007) Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain 128(3):199–208

    Article  CAS  PubMed  Google Scholar 

  29. Riva R, Mork PJ, Westgaard RH, Okkenhaug Johansen T, Lundberg U (2012) Catecholamines and heart rate in female fibromyalgia patients. J Psychosom Res 72(1):51–57

    Article  PubMed  Google Scholar 

  30. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y et al (2003) COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 299(5610):1240–1243

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a Korea University Grant.

Conflict of interest

The authors have no financial or non-financial conflict of interest to declare.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, Korea

    Young Ho Lee, Jae-Hoon Kim & Gwan Gyu Song

Authors
  1. Young Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jae-Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gwan Gyu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, Y.H., Kim, JH. & Song, G.G. Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis. Rheumatol Int 35, 159–166 (2015). https://doi.org/10.1007/s00296-014-3075-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-014-3075-2

Keywords

Search

Navigation