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Matrix Metalloproteinase-3, Vitamin D Receptor Gene Polymorphisms, and Occupational Risk Factors in Lumbar Disc Degeneration

Journal of Occupational Rehabilitation volume 24, pages 370–381 (2014)Cite this article

Abstract

Background Lumbar disc degeneration (LDD) is a process that begins early in life, contributing to the development of low back pain. LDD is a consequence of a variety of factors, and its etiology remains poorly understood. Objectives to investigate occupational and genetic risk factors inducing lumbar disc degeneration, and to evaluate the possible association of genetic polymorphisms of matrix metalloproteinase 3 (MMP-3) and vitamin D receptor (VDR) with the severity of LDD in an Egyptian population. Subjects and Methods A case control study involving 84 LDD and 60 controls was carried out. Five types of work related factors were investigated by questionnaire, complete neurological examination for all subjects and MRI for the cases. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect polymorphisms in MMP-3 Promoter (−1,171 6A/5A) (rs 731236) and VDR-Apa (rs 35068180). Results We found that family history, back injury, smoking, high level of sitting, bending/twisting, physical workload, lifting, whole body vibration, mutant allele 5A of MMP-3 and mutant allele T of VDR were significantly associated with LDD (OR = 2.9, 3.1, 2.1, 11.1, 15.9, 11.7, 8.2, 12.6, 2.5 and 3.1 respectively, p < 0.05). Cases that carry allele 5A and/or allele T were associated with LDD severity. Conclusion LDD is closely associated in occurrence and severity with occupational, environmental risk factors and susceptibility genes namely MMP-3, and VDR (ApaI). This study throws light on the importance of screening for early detection of susceptible individuals and disease prevention.

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References

  1. Taher F, Essig DR, Lebl DR, Hughes AP, Sama AA, Cammisa FP, Girardi FP. Lumbar degenerative disc disease: current and future concepts of diagnosis and management. Adv Orthop. 2012;. doi:10.1155/2012/970752.

    PubMed Central  PubMed  Google Scholar 

  2. Freemont AJ. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology. 2009;48:5–10.

    CAS  PubMed  Article  Google Scholar 

  3. Yaun HY, Tang Y, Liang Y, Lei L, Xiao G, Wang S, Xia Z. Matrix metalloproteinase-3 and vitamin D receptor genetic polymorphism, and their interaction with occupational exposure in lumbar disc degeneration. J Occup Health. 2010;52:23–30.

    Article  Google Scholar 

  4. Williams F, Sambrook P. Neck and back pain and intervertebral disc degeneration: role of occupational factors. Best Pract Res. 2011;25(1):69–79.

    CAS  Article  Google Scholar 

  5. Kalichman L, Hunter DJ. The genetics of intervertebral disc degeneration associated genes. Joint Bone Spine. 2008;75(4):388–96.

    CAS  PubMed  Article  Google Scholar 

  6. Gallieni M, Cozzolino M, Fallabrino G, Pasho S, Olivi L, Brancaccio D, et al. Physiology and pathophysiology. Int J Artif Organs. 2009;32:87–94.

    CAS  PubMed  Google Scholar 

  7. Michaelsson K, Wolk A, Jacobsson A, Kindmark A, Grundberg E, Stiger F, Mallmin H, et al. The positive effect of dietary vitamin D intake on bone mineral density in men is modulated by the polyadenosine repeat polymorphism of the vitamin D receptor. Bone. 2006;39:1343–51.

    CAS  PubMed  Article  Google Scholar 

  8. Colombini A, Cauci S, Lombardi G, Lanteri P, Croiset S, Brayda-Bruno M, Banfi G. Relationship between vitamin D receptor gene (VDR) polymorphisms, vitamin D status, osteoarthritis and intervertebral disc degeneration (Review). J Steroid Biochem Mol Biol. 2013;138:24–40.

    CAS  PubMed  Article  Google Scholar 

  9. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA. Prediction of bone density from vitamin D receptor alleles. Nature. 1994;367:284–7.

    CAS  PubMed  Article  Google Scholar 

  10. Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA. Vitamin D receptor gene polymorphisms in relation to vitamin D related disease states. J Steroid Biochem Mol Biol. 2004;89:187–93.

    PubMed  Article  Google Scholar 

  11. Ogunkolade BW, Boucher BJ, Prahl JM, Bustin SA, Burrin JM, Noonan K, North BV, et al. Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians. Diabetes. 2002;51:2294–300.

    CAS  PubMed  Article  Google Scholar 

  12. Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006;371:1–12.

    CAS  PubMed  Article  Google Scholar 

  13. Priestley L, Fergusson C, Ogilvie D, Wordsworth P, Smith R, Pattrick M, Doherty M, Sykes B. A limited association of generalized osteoarthritis with alleles at the type II collagen locus: cOL2A1. Br J Rheumatol. 1991;30(4):272–5.

    CAS  PubMed  Article  Google Scholar 

  14. Takahashi M, Haro H, Wakabayashi Y, Kawa-uchi T, Komori H, Shinomiya K. The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene. J Bone Joint Surg (Br). 2001;83-B: 491–5.

    Google Scholar 

  15. Omair A, Holden M, Alexandra ML, Olav Reikeras O, Brox JI. Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants: a prospective genetic association study. BMC Musculoskelet Disord. 2013;14:105.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  16. World Medical Association Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Revised by the 52nd WMA General Assembly, Edinburgh, Scotland. October 2000. http://www.wma.net/e/policy/b3.htm.

  17. Wiktorin C, Hjelm EW, Winkel J, Köster M. Reproducibility of a questionnaire for assessment of physical load during work and leisure time. Stockholm MUSIC 1 study group. MUSculoskeletal Intervention Center. J Occup Environm Med. 1996;38:190–201.

    Google Scholar 

  18. NIOSH. National Institute of Occupational Safety and Health. National Occupational Research agenda for musculoskeletal disorders, DHHS (NIOSH) publications No. 2001-117-Cincinnati: DHHS, NIOSH; 2001.

  19. Devillé WL, van der Windt DA, Dzaferagić A, Bezemer PD, Bouter LM. The test of Lasègue: systematic review of the accuracy in diagnosing herniated discs. Spine. 2000;25(9):1140–7.

    PubMed  Article  Google Scholar 

  20. Kettler A, Wilke HJ. Review of existing grading systems for cervical or lumbar disc and facet joint degeneration. Eur Spine J. 2006;15(6):705–18.

    PubMed Central  PubMed  Article  Google Scholar 

  21. Vairaktaris E, Yapijakis C, Vasiliou S, Derka S, Nkenke E, Serefoglou Z, et al. Association of −1171 promoter polymorphism of matrix metalloproteinase-3 with increased risk for oral cancer. Anticancer Res. 2007;27(6B):4095–100.

    Google Scholar 

  22. Carless MA, Kraska T, Lintell N, Neale RE, Green AC, Griffiths LR. Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin. Br J Dermatol. 2008;159(4):804–10.

    CAS  PubMed  Article  Google Scholar 

  23. Seidler A, Bolm-Audorff U, Siol T, Henkel N, Fuchs C, Schug C, et al. Occupational risk factors for symptomatic lumbar disc herniation; a case-control study. Occup Environ Med. 2003;60:821–30.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  24. Seidler A, Bergmann A, Jäger M, Ellegast W, et al. Cumulative occupational lumbar load and lumbar disc disease—results of a German multi-center case-control study (EPILIFT). BMC Musculoskelet Disord. 2009;10:48. doi:10.1186/1471-2474-10-48.

    PubMed Central  PubMed  Article  Google Scholar 

  25. Adams MA, McNally DS, Dolan P. Stress distributions inside intervertebral discs. The effects of age and degeneration. J Bone Joint Surg Br. 1996;78:965–72.

    CAS  PubMed  Article  Google Scholar 

  26. Iatridis JC, Mente PL, Stokes IA, Aronsson DD, Alini M. Compression- induced changes in intervertebral disc properties in a rat tail model. Spine. 1999;24:996–1002.

    CAS  PubMed  Article  Google Scholar 

  27. Keller TS, Hansson TH, Holm S, Pope MH, Spengler DM. In vivo creep behavior of the normal and degenerated porcine intervertebral disc: a preliminary report. J Spinal Disord. 1988;1:267–78.

    CAS  PubMed  Google Scholar 

  28. Hadjipavlou AG, Tzermiadianos MN, Bogduk N, et al. The pathophysiology of disc degeneration: a critical review. J Bone Joint Surg Br. 2008;90:1261.

    CAS  PubMed  Article  Google Scholar 

  29. Zhang Y, Zhang F, Sun Z, Guo W, Liu J, Liu M, Guoy X. A controlled case study of the relationship between environmental risk factors and apoptotic gene polymorphism and lumbar disc herniation. Am J Pathol. 2013;182:56–63.

    CAS  PubMed  Article  Google Scholar 

  30. Mohammed A, Anil K, Bobby Y, Abhinav S, Mike W, Allen G. Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration. Spine. 2004;29:568–75.

    Article  Google Scholar 

  31. Battie MC, Videman T, Gill K, Moneta A, Giovannil B, Nyman R, Kaprio J, Koskenvuo M. Volvo award in clinical sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins. Spine. 1991;16:1015–21.

    CAS  PubMed  Article  Google Scholar 

  32. Oda H, Matsuzaki Y, Wakabayash K, Uematsu Y, Iwashi M. Degeneration of intervertebral discs due to smoking: experimental assessment in a rat- smoking model. J Orthop Sci. 2004;9:135–41.

    CAS  PubMed  Article  Google Scholar 

  33. Nunes FT, Conforti-Froes ND, Negrelli WF, Souza DRS. Genetic and environmental factors involved in intervertebral disc degeneration. Acta Ortop Bras. 2007;15(1):9–13.

    Google Scholar 

  34. Varlotta GP, Brown MD, Kelsey JI, Golden AL. Familial predisposition for herniation of a lumbar disc in patients who are less than twenty one years old. J Bone Joint Surg (Am). 1991;73:124–8.

    CAS  Google Scholar 

  35. Riihimaki H, Viikari-Juntura E, Moneta G, Kuha J, Videman T, Tola S. Incidence of sciatic pain among men in machine operating, dynamic physical work, and sedentary work: a three-year follow-up. Spine. 1994;19(2):138–42.

    CAS  PubMed  Article  Google Scholar 

  36. Weiler C, Nerlich AG, Zipperer J, Bachmeier BE, Boos N. SSE award competition in basic science: expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Eur Spine J. 2002;11(4):308–20.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  37. Ye S, Eriksson P, Hamsten A, Humphries SE, Henney AM. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem. 1996;271:13055–60.

    CAS  PubMed  Article  Google Scholar 

  38. Bijerk C, Houwing-Duistermaat JJ, Valkenberg HA. Heritability of radiologic osteoarthritis in peripheral joints and of disc degeneration of the spine. Arthritis Rheum. 1999;42:1729–35.

    Article  Google Scholar 

  39. Terashima M, Akita H, Kanazawa K, et al. Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction. Circulation. 1999;99:2717–9.

    CAS  PubMed  Article  Google Scholar 

  40. Colombini A, Lanteri P, Lombardi G, Grasso D, Recordati C, Lovi A, Banfi G, et al. Metabolic effects of vitamin D active metabolites in monolayer and micromass cultures of nucleus pulposus and annulus fibrosus cells isolated from human intervertebral disc. Int J Biochem Cell Biol. 2012;44(6):1019–30.

    CAS  PubMed  Article  Google Scholar 

  41. Videman T, Leppavuori J, Kaprio J. Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine. 1998;23:2477–85.

    CAS  PubMed  Article  Google Scholar 

  42. Balmain N, Hauchecorne M, Pike JW, Cuisinier-Gleizes P, Mathieu H. Distribution and subcellular immunolocalization of 1, 25-dihydroxyvitamin D3 receptors in rat epiphyseal cartilage. Cell Mol Biol (Noisy-le-grand).1993;39:339–50.

    Google Scholar 

  43. Gruber HE, Hoelscher G, Ingram JA, Chow Y, Loeffle B, Hanley EN. 1,25(OH)2-vitamin D3 inhibits proliferation and decreases production of monocyte chemoattractant protein-1, thrombopoietin, VEGF, and angiogenin by human annulus cells in vitro. Spine 2008;33(7):755–65.

    Google Scholar 

  44. Wang ZC, Chen XS, Wang DW, Shi JG, Jia LS, Xu GH. The genetic association of vitamin D receptor polymorphisms and cervical spondylotic myelopathy in Chinese subjects. Clin Chim Acta. 2010;411:794–7.

    CAS  PubMed  Article  Google Scholar 

  45. Pockert AJ, Richardson SM, Le Maitre CL, Lyon M, Deakin JA, et al. Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis Rheum. 2009;60(2):482–91.

    CAS  PubMed  Article  Google Scholar 

  46. Maksymowych WP, Landewe R, Conner-Spady B, Dougados M, Mielants H, van der Tempel H, Poole AR, et al. Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis. Arthritis Rheum. 2007;56(6):1846–53.

    CAS  PubMed  Article  Google Scholar 

  47. Valdes AM, Hassett G, Hart D, Spector T. Radiographic progression of lumbar spine disc degeneration is influenced by variation at inflammatory genes: a candidate SNP association study in the chingford cohort. Spine. 2005;30:2445–51.

    PubMed  Article  Google Scholar 

  48. Kawaguchi Y, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T. The association of lumbar disc disease with vitamin-D receptor gene polymorphism. J Bone Joint Surg Am. 2002;84A:2022–8.

    Google Scholar 

  49. Lee Y, Woo J, Choi S, Ji J, Song G. Vitamin D receptor TaqI, BsmI and ApaI polymorphisms and osteoarthritis susceptibility: a meta-analysis. Joint Bone Spine. 2009;76:156–61.

    CAS  PubMed  Article  Google Scholar 

  50. Lorentzon M, Lorentzon R, Nordström P.Vitamin D receptor gene polymorphism is related to bone density, circulating osteocalcin, and parathyroid hormone in healthy adolescent girls. Bone Miner Metab. 2001;19:302–7.

    Google Scholar 

  51. Kepler CK, Ponnappan RK, Tannoury CA, Risbud MV, Anderson DG. The molecular basis of intervertebral disc degeneration. Spine. 2013;13(3):318–30.

    Article  Google Scholar 

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Author information

Affiliations

  1. Occupational and Environmental Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt

    N. H. Zawilla, N. Mansour & S. Helal

  2. Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Giza, Egypt

    H. Darweesh & R. El Shazly

  3. Medical Biochemistry Department, Faculty of Medicine, Cairo University, Giza, Egypt

    F. M. Taha

  4. Radiology Department, Faculty of Medicine, Cairo University, Giza, Egypt

    M. Awadallah

Authors
  1. N. H. Zawilla
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  2. H. Darweesh
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Correspondence to N. H. Zawilla.

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Zawilla, N.H., Darweesh, H., Mansour, N. et al. Matrix Metalloproteinase-3, Vitamin D Receptor Gene Polymorphisms, and Occupational Risk Factors in Lumbar Disc Degeneration. J Occup Rehabil 24, 370–381 (2014). https://doi.org/10.1007/s10926-013-9472-7

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  • DOI: https://doi.org/10.1007/s10926-013-9472-7

Keywords

  • Lumbar disc degeneration
  • Occupational risk factors
  • MMP3
  • VDR