Skip to main content

Advertisement

SpringerLink
Log in

COMT and SCN9A gene variants do not contribute to chronic low back pain in Mexican-Mestizo patients

  • Original Article
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

Chronic low back pain (CLBP) is a complex condition in which genetic factors play a role in its susceptibility. Catechol-O-methyltransferase (COMT) and sodium channel NaV1.7 (SCN9A) genes are implicated in pain perception. The aim is to analyze the association of COMT and SCN9A with CLBP and their interaction, in a Mexican-Mestizo population.

Methods

A case–control study was conducted. Cases corresponded to adults of both sexes with CLBP. Controls were adults with no CLBP. Variants of SCN9A and COMT were genotyped. Allelic and genotypic frequencies and Hardy–Weinberg equilibrium (HWE) were calculated. Association was tested under codominant, dominant, and recessive models. Multifactor dimensionality reduction was developed to detect epistasis.

Results

Gene variants were in HWE, and there was no association under different inheritance models in the whole sample. In women, in codominant and dominant models, a trend to a high risk was observed for AA of rs4680 of COMT (OR = 1.7 [0.5–5.3] and 1.6 [0.7–3.4]) and for TT of rs4633 (OR = 1.6 [0.7–3.7] and 1.6 [0.7–3.4]). In men, a trend to low risk was observed for AG genotype of rs4680 in the same models (OR = 0.6 [0.2–1.7] and 0.7 [0.3–1.7]), and for TC genotype of rs4633 in the codominant model (OR = 0.6 [0.2–1.7]). In the interaction analysis, a model of the SCN9A and COMT variants showed a CVC of 10/10; however, the TA was 0.4141.

Conclusion

COMT and SCN9A variants are not associated with CLBP in the analyzed Mexican-Mestizo population.

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

Similar content being viewed by others

Data availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”.

Abbreviations

CLBP:

Chronic low back pain

COMT :

Catechol-O-methyltransferase

CVC:

Cross-validation consistency

HWE:

Hardy-Weinberg equilibrium

MDR:

Multifactor dimensionality reduction

MPQ:

McGill pain questionnaire short form

SCN9A :

Sodium channel NaV1.7

TA:

Testing accuracy

References

  1. Baumbauer KM, Ramesh D, Perry M, Carney KB, Julian T, Glidden N, Dorsey SG, Starkweather AR, Young EE (2020) Contribution of COMT and BDNF genotype and expression to the risk of transition from acute to chronic low back pain. Clin J Pain. https://doi.org/10.1097/AJP.0000000000000819

    Article  PubMed  PubMed Central  Google Scholar 

  2. Belfer I, Segall S (2011) COMT genetic variants and pain. Drugs Today (Barc) 47(6):457–467

    Article  CAS  PubMed  Google Scholar 

  3. Belfer I, Segall SK, Lariviere WR et al (2013) Pain modality- and sex-specific effects of COMT genetic functional variants. Pain 154(8):1368–1376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bjorland S, Røe C, Moen A, Schistad E, Mahmood A, Gjerstad J (2017) Genetic predictors of recovery in low back and lumbar radicular pain. Pain 158(8):1456–1460

    Article  PubMed  Google Scholar 

  5. Brancher JA, Bertoli FM de P, Michels B, Lopes-Faturri A, Pizzatto E, Losso EM, Orsi JS, Feltrin de Souza J, Küchler EC, Wambier LM (2021) Is catechol-O-methyltransferase gene associated with temporomandibular disorders? A systematic review and meta-analysis. Int J Paediatr Dent 31(1):152–163

  6. Chen J, Lipska BK, Halim N et al (2004) Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75(5):807–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cook CE, Taylor J, Wright A, Milosavljevic S, Goode A, Whitford M (2014) Risk factors for first time incidence sciatica: a systematic review. Physiother Res Int 19(2):65–78

    Article  PubMed  Google Scholar 

  8. Dai F, Belfer I, Schwartz CE, Banco R, Martha JF, Tighioughart H, Tromanhauser SG, Jenis LG, Kim DH (2010) Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. Spine J 10(11):949–957

    Article  PubMed  Google Scholar 

  9. Diatchenko L, Fillingim RB, Smith SB, Maixner W (2013) The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol 9(6):340–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Do Carmo Silva Parreira P, Maher CG, Latimer J, Steffens D, Blyth F, Li Q, Ferreira ML (2015) Can patients identify what triggers their back pain? Secondary analysis of a case-crossover study. Pain 156(10):1913–1919

  11. Estacion M, Harty TP, Choi JS, Tyrrell L, Dib-Hajj SD, Waxman SG (2009) A sodium channel gene SCN9A polymorphism that increases nociceptor excitability. Ann Neurol 66(6):862–866

    Article  CAS  PubMed  Google Scholar 

  12. Ferreira PH, Beckenkamp P, Maher CG, Hopper JL, Ferreira ML (2013) Nature or nurture in low back pain? Results of a systematic review of studies based on twin samples. Eur J Pain 17(7):957–971

    Article  CAS  PubMed  Google Scholar 

  13. Frymoyer JW, Pope MH, Clements JH, Wilder DG, MacPherson B, Ashikaga T (1983) Risk factors in low-back pain. An epidemiological survey. J Bone Joint Surg Am 65(2):213–218

    Article  CAS  PubMed  Google Scholar 

  14. Glass TA, Goodman SN, Hernán MA, Samet JM (2013) Causal inference in public health. Annu Rev Public Health 34:61–75

    Article  PubMed  PubMed Central  Google Scholar 

  15. Gorodezky C, Alaez C, Vázquez-García MN, De La Rosa G, Infante E, Balladares S, Toribio R, Pérez-Luque E, Muñoz L (2001) The genetic structure of Mexican Mestizos of different locations: tracking back their origins through MHC genes, blood group systems, and microsatellites. Hum Immunol 62(9):979–991

    Article  CAS  PubMed  Google Scholar 

  16. Gruber HE, Sha W, Brouwer CR, Steuerwald N, Hoelscher GL, Hanley EN (2014) A novel catechol-O-methyltransferase variant associated with human disc degeneration. Int J Med Sci 11(7):748–753

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hartvigsen J, Hancock MJ, Kongsted A et al (2018) What low back pain is and why we need to pay attention. Lancet 391(10137):2356–2367

    Article  PubMed  Google Scholar 

  18. I T, J L, (2009) Current evidence for a modulation of low back pain by human genetic variants. J Cell Mol Med 13(8B):1605–1619

    Article  Google Scholar 

  19. Jacobsen LM, Schistad EI, Storesund A, Pedersen LM, Rygh LJ, Røe C, Gjerstad J (2012) The COMT rs4680 Met allele contributes to long-lasting low back pain, sciatica and disability after lumbar disc herniation. Eur J Pain 16(7):1064–1069

    Article  CAS  PubMed  Google Scholar 

  20. Janssen LP, Medeiros LF, de Souza A, da Silva J (2021) Fibromyalgia: a review of related polymorphisms and clinical relevance. An Acad Bras Cienc. https://doi.org/10.1590/0001-3765202120210618

    Article  PubMed  Google Scholar 

  21. Kamaleri Y, Natvig B, Ihlebaek CM, Bruusgaard D (2009) Does the number of musculoskeletal pain sites predict work disability? A 14-year prospective study. Eur J Pain 13(4):426–430

    Article  PubMed  Google Scholar 

  22. Knezevic NN, Candido KD, Vlaeyen JWS, Van Zundert J, Cohen SP (2021) Low back pain. The Lancet 398(10294):78–92

    Article  Google Scholar 

  23. Knezevic NN, Tverdohleb T, Knezevic I, Candido KD (2018) The role of genetic polymorphisms in chronic pain patients. Int J Mol Sci. https://doi.org/10.3390/IJMS19061707

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kurzawski M, Rut M, Dziedziejko V, Safranow K, Machoy-Mokrzynska A, Drozdzik M, Bialecka M (2018) Common missense variant of SCN9A gene is associated with pain intensity in patients with chronic pain from disc herniation. Pain Med 19(5):1010–1014

    Article  PubMed  Google Scholar 

  25. Melzack R (1987) The short-form McGill Pain Questionnaire. Pain 30(2):191–197

    Article  PubMed  Google Scholar 

  26. Moore JH, Gilbert JC, Tsai CT, Chiang FT, Holden T, Barney N, White BC (2006) A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J Theor Biol 241(2):252–261

    Article  MathSciNet  PubMed  ADS  Google Scholar 

  27. Moreno-Estrada A, Gignoux CR, Fernández-López JC et al (1979) (2014) The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344(6189):1280–1285

    Article  ADS  Google Scholar 

  28. Motsinger AA, Ritchie MD (2006) Multifactor dimensionality reduction: an analysis strategy for modelling and detecting gene-gene interactions in human genetics and pharmacogenomics studies. Hum Genomics 2(5):318–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nagel RL (2005) Epistasis and the genetics of human diseases. C R Biol 328(7):606–615

    Article  CAS  PubMed  Google Scholar 

  30. Omair A, Lie BA, Reikeras O, Holden M, Brox JI (2012) Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic association study. BMC Musculoskelet Disord. https://doi.org/10.1186/1471-2474-13-76

    Article  PubMed  PubMed Central  Google Scholar 

  31. Omair A, Mannion AF, Holden M, Fairbank J, Lie BA, Hägg O, Fritzell P, Brox JI (2015) Catechol-O-methyltransferase (COMT) gene polymorphisms are associated with baseline disability but not long-term treatment outcome in patients with chronic low back pain. Eur Spine J 24(11):2425–2431

    Article  PubMed  Google Scholar 

  32. Reimanna F, Cox JJ, Belfer I, et al (2010) Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci U S A 107(11):5148–5153

  33. Rut M, Machoy-Mokrzyńska A, Rȩcławowicz D, Słoniewski P, Kurzawski M, Droadzik M, Safranow K, Morawska M, Białecka M (2014) Influence of variation in the catechol-O-methyltransferase gene on the clinical outcome after lumbar spine surgery for one-level symptomatic disc disease: a report on 176 cases. Acta Neurochir (Wien) 156(2):245–252

    Article  PubMed  Google Scholar 

  34. Sadamasu A, Sakuma Y, Suzuki M, et al (2014) Upregulation of NaV1.7 in dorsal root ganglia after intervertebral disc injury in rats. Spine (Phila Pa 1976). https://doi.org/10.1097/BRS.0000000000000229

  35. Smith SB, Reenilä I, Männistö PT, Slade GD, Maixner W, Diatchenko L, Nackley AG (2014) Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain. Pain 155(11):2390–2399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Taylor JB, Goode AP, George SZ, Cook CE (2014) Incidence and risk factors for first-time incident low back pain: a systematic review and meta-analysis. Spine J 14(10):2299–2319

    Article  PubMed  Google Scholar 

  37. Vargas-Alarcon G, Alvarez-Leon E, Fragoso JM, Vargas A, Martinez A, Vallejo M, Martinez-Lavin M (2012) A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia. BMC Musculoskelet Disord. https://doi.org/10.1186/1471-2474-13-23

    Article  PubMed  PubMed Central  Google Scholar 

  38. Vlaeyen JWS, Maher CG, Wiech K, Van Zundert J, Meloto CB, Diatchenko L, Battié MC, Goossens M, Koes B, Linton SJ (2018) Low back pain. Nat Rev Dis Primers 4(1):52

    Article  PubMed  Google Scholar 

  39. Von Korff M, Crane P, Lane M, Miglioretti DL, Simon G, Saunders K, Stang P, Brandenburg N, Kessler R (2005) Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication. Pain 113(3):331–339

    Article  Google Scholar 

  40. Vossen H, Kenis G, Rutten B, van Os J, Hermens H, Lousberg R (2010) The genetic influence on the cortical processing of experimental pain and the moderating effect of pain status. PLoS One. https://doi.org/10.1371/JOURNAL.PONE.0013641

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wacholder S, Mclaughlin JK, Silverman DT, Mandel JS (1992) Selection of controls in case-control studies: I. Principles Am J Epidemiol 135(9):1019–1028

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedic Rehabilitation, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Av. México-Xochimilco 289, Colonia Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico

    Tania Inés Nava-Bringas

  2. Department of Genomic Medicine, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Av. México-Xochimilco 289, Colonia Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico

    Carlos Manuel Juaristi Manrique, Norma Celia González-Huerta & Antonio Miranda-Duarte

  3. Radiology Service, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Av. México-Xochimilco 289, Colonia Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico

    Eugenio Morales-Hernández

Authors
  1. Tania Inés Nava-Bringas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos Manuel Juaristi Manrique
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Norma Celia González-Huerta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eugenio Morales-Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Miranda-Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TIN-B and AM-D contributed to the study conception and design. Material preparation and data collection were performed by TIN-B, CMJM, NCG-H, and EM-H. Analysis was performed by AM-D. The first draft of the manuscript was written by TIN-B and AM-D, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Antonio Miranda-Duarte.

Ethics declarations

Ethics approval

All procedures performed in the participants were in accordance with the ethical standards of the Ethics and Investigation Committee of the Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra” (registry number 49/11), and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all participants.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 331 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nava-Bringas, T.I., Manrique, C.M.J., González-Huerta, N.C. et al. COMT and SCN9A gene variants do not contribute to chronic low back pain in Mexican-Mestizo patients. Acta Neurochir 166, 73 (2024). https://doi.org/10.1007/s00701-024-05937-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00701-024-05937-y

Keywords

Search

Navigation