Analysis of genetic polymorphisms associated with intervertebral disc degeneration

Serkan Kitis; Zeynep Mine Coskun; Pelin Tasdemir; Ebru Tuncez; Ayse Gul Zamani; Aynur Acar

doi:10.14715/cmb/2018.64.10.10

Issue

Vol. 64 No. 10: Issue 10

Issue Published : August 3, 2018

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Analysis of genetic polymorphisms associated with intervertebral disc degeneration

https://doi.org/10.14715/cmb/2018.64.10.10

Serkan Kitis

Department of Neurosurgery, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey

Zeynep Mine Coskun

Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istanbul Bilim University, Istanbul, Turkey

Pelin Tasdemir

Department of Medical Genetic, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey

Ebru Tuncez

Medical Genetic Section, Sanlıurfa Training and Research Hospital, Sanlıurfa, Turkey

Ayse Gul Zamani

Department of Medical Genetic, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey

Aynur Acar

Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istanbul Bilim University, Istanbul, Turkey

Corresponding Author(s) : Zeynep Mine Coskun

zeynepminecoskun@gmail.com

Cellular and Molecular Biology, Vol. 64 No. 10: Issue 10
Article Published : July 30, 2018

Abstract

Intervertebral disc degeneration (IVDD) is a common degenerative spinal condition. Recent studies have shown that the incidence of disc herniation and disc degeneration may be explained by genetic factors. In this study, we investigated the link between various polymorphic variants of the vitamin D receptor (VDR), matrix metalloproteinase 2 (MMP2), and insulin like growth factor 1 receptor (IGF1R) genes and IVDD in patients with IVDD, in Turkey. We examined and genotyped 199 patients with IVDD and 197 healthy individuals. Genomic DNA was isolated from the peripheral blood leukocytes of all participants, and analyzed using real-time PCR. Via melting curve analysis, VDR, MMP2, and IGF1R polymorphism variant distributions were determined. The patients with IVDD showed higher frequencies of the VDR ApaI A allele genotype as compared to the control group; however, there were no significant differences in the frequencies or allelic distributions of the IGF1R and MMP2 genotypes between the IVDD patients and the control group. The incidence of IVDD in these Turkish patients is correlated with the VDR ApaI gene polymorphism, but not with the IGF1R and MMP2 polymorphisms.

Keywords

Insulin like growth factor 1 receptor Intervertebral disc degeneration Matrix metalloproteinase-2 Polymorphism Vitamin D receptor.

Kitis, S., Coskun, Z. M., Tasdemir, P., Tuncez, E., Zamani, A. G., & Acar, A. (2018). Analysis of genetic polymorphisms associated with intervertebral disc degeneration. Cellular and Molecular Biology, 64(10), 61–65. https://doi.org/10.14715/cmb/2018.64.10.10

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References

Hughes SP, Freemont AJ, Hukins DW, McGregor AH, Roberts S. The pathogenesis of degeneration of the intervertebral disc and emerging therapies in the management of back pain. J Bone Joint Surg Br 2012;94(10):1298-304.
Hoy D, March L, Brooks P, Blyth F, Woolf A, Bain C, et al. The global burden of low back pain: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73(6):968-74.
Cortes DH, Elliott DM. Molecular and structural studies of the disc in health and disease. In: Shapiro IM, Risbud MV, editor. The intervertebral disc: Overview of disc mechanics. Vienna: Springer; 2014. 17-31 p.
Daly C, Ghosh P, Jenkin G, Oehme D, Goldschlager T. A review of animal models of ıntervertebral disc degeneration: pathophysiology, regeneration, and translation to the clinic. Biomed Res Int 2016; 2016:5952165.
Zhang F, Zhao X, Shen H, Zhang C. Molecular mechanisms of cell death in intervertebral disc degeneration (Review). Int J Mol Med 2016; 37(6):1439-1448.
Adams MA. Intervertebral disc tissues. In: Derby B, Akhtar R, editor. Mechanical properties of aging soft tissues, engineering materials and processes. Switzerland: Springer International Publishing; 2015.
Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 2001; 26:1873-8.
Yu LP, Qian WW, Yin GY, Ren YX, Hu ZY. MRI assessment of lumbar intervertebral disc degeneration with lumbar degenerative disease using the Pfirrmann grading systems. PLoS One 2012; 7(12):e48074.
Shankar H, Scarlett JA, Abram SE. Anatomy and pathophysiology of intervertebral disc disease. Tech Reg Anesth and Pain Manag 2009; 13(2):67-75.
Kalb S, Martirosyan LN, Kalani YS, Boc GG, Theodore N. Genetics of the degenerated intervertebral disc. World Neurosurgery 2012; 77(3/4):491-501.
Nong L, Huang Y, Zhao S, Xu N. Vitamin D receptor gene, matrix metalloproteinase 3 polymorphisms and the risk of ıntervertebral disc degeneration susceptibility: meta-analysis. Asian Spine J 2016; 10(5):964-71.
Kalichman L, Hunter DJ. The genetics of intervertebral disc degeneration. Associated genes. Joint Bone Spine 2008; 75:388-96.
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; 84-A(11):2022-8.
Urano T, Narusawa K, Shiraki M, Usui T, Sasaki N, Hosoi T, et al. Association of a single nucleotide polymorphism in the insulin-like growth factor-1 receptor gene with spinal disc degeneration in postmenopausal Japanese women. Spine (Phila Pa 1976) 2008; 33:1256-1.
Dong DM, Yao M, Liu B, Sun CY, Jiang YQ, Wang YS. Association between the -1306C/T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults. Eur Spine J 2007; 16(11):1958-61.
Elmasry S, Asfour S, de Rivero Vaccari JP, Travascio F. Effects of tobacco smoking on the degeneration of the ıntervertebral disc: a finite element study. PLoS One 2015; 10(8):e0136137.
Akmal M, Kesani A, Anand B, Singh A, Wiseman M, Goodship A. Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration. Spine 2004; 29568-75.
Zawilla NH, Darweesh H, Mansour N, Helal S, Taha FM, Awadallah M, et al. Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration. J Occup Rehabil 2014; 24:370-81.
Rajasekaran S, Kanna RM, Reddy RR, Natesan S, Raveendran M, Cheung KM, et al. How Reliable Are the Reported Genetic Associations in Disc Degeneration?: The Influence of Phenotypes, Age, Population Size, and Inclusion Sequence in 809 Patients. Spine (Phila Pa 1976) 2016; 41(21):1649-60.
Carlberg C, Molnar F. Detailed molecular understanding of agonistic and antagonistic vitamin D receptor ligands. Curr Top Med Chem 2006; 6:1243-53.
Cheung KM, Chan D, Karppinen J, Chen Y, Jim JJ, Yip SP, et al. Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population. Spine (Phila Pa 1976) 2006; 31:1143-8.
Mayer JE, Iatridis JC, Chan D, Qureshi SA, Gottesman O, Hecht AC. Genetic polymorphisms associated with intervertebral disc degeneration. Spine J 2013; 13(3): 299-317.
Li Y, Zhu J, Gao C, Peng B. Vitamin D receptor (VDR) genetic polymorphism associated with intervertebral disc degeneration. J Genet Genomics 2015; 42:135-40.
Colombini A, Brayda-Bruno M, Lombardi G, Croiset SJ, Ceriani C, Buligan C, et al. BsmI, ApaI and TaqI Polymorphisms in the vitamin D receptor Gene (VDR) and association with Lumbar spine pathologies: An Italian case-control study. PLoS One 2016; 11(5):e0155004.
Crean JK, Roberts S, Jaffray DC, Eisenstein SM, Duance VC. Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis. Spine (Phila Pa 1976) 1997; 22(24):2877-84.
Weiler C, Nerlich AG, Zipperer J. 2002 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.
Rutges JP, Kummer JA, Oner FC, Verbout AJ, Castelein RJ, Roestenburg HJ, et al. Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels. J Pathol 2008; 214(4):523-30.
Price SJ, Greaves DR, Watkins H. Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem 2001; 276:7549-58.
Martirosyan NL, Patel AA, Carotenuto A, Kalani MY, Belykh E, Walker CT, et al. Genetic Alterations in Intervertebral Disc Disease. Front Surg 2016; 3:59.
Goodrich LR, Hidaka C, Robbins PD, Evans CH, Nixon AJ. Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model. J Bone Joint Surg Br 2007; 89:672-85.
Pattison ST, Melrose J, Ghosh P, Taylor TK. Regulation of gelatinase-A (MMP-2) production by ovine intervertebral disc nukleus pulposus cells grown in alginate bead culture by Transforming Growth Factor-beta(1)and insulin like growth factor-I. Cell Biol Int 2001; 25:679-89.
Nerlich AG, Bachmeier BE, Boos N. Expression of fibronectin and TGF-beta1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue. Eur Spine J 2005; 14:17-26.
Li B, Zheng XF, Ni BB, Yang YH, Jiang SD, Lu H, et al. Reduced expression of insulin-like growth factor 1 receptor leads to accelerated intervertebral disc degeneration in mice. Int J Immunopathol Pharmacol 2013; 26(2):337-47.

References

Hughes SP, Freemont AJ, Hukins DW, McGregor AH, Roberts S. The pathogenesis of degeneration of the intervertebral disc and emerging therapies in the management of back pain. J Bone Joint Surg Br 2012;94(10):1298-304.

Hoy D, March L, Brooks P, Blyth F, Woolf A, Bain C, et al. The global burden of low back pain: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73(6):968-74.

Cortes DH, Elliott DM. Molecular and structural studies of the disc in health and disease. In: Shapiro IM, Risbud MV, editor. The intervertebral disc: Overview of disc mechanics. Vienna: Springer; 2014. 17-31 p.

Daly C, Ghosh P, Jenkin G, Oehme D, Goldschlager T. A review of animal models of ıntervertebral disc degeneration: pathophysiology, regeneration, and translation to the clinic. Biomed Res Int 2016; 2016:5952165.

Zhang F, Zhao X, Shen H, Zhang C. Molecular mechanisms of cell death in intervertebral disc degeneration (Review). Int J Mol Med 2016; 37(6):1439-1448.

Adams MA. Intervertebral disc tissues. In: Derby B, Akhtar R, editor. Mechanical properties of aging soft tissues, engineering materials and processes. Switzerland: Springer International Publishing; 2015.

Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 2001; 26:1873-8.

Yu LP, Qian WW, Yin GY, Ren YX, Hu ZY. MRI assessment of lumbar intervertebral disc degeneration with lumbar degenerative disease using the Pfirrmann grading systems. PLoS One 2012; 7(12):e48074.

Shankar H, Scarlett JA, Abram SE. Anatomy and pathophysiology of intervertebral disc disease. Tech Reg Anesth and Pain Manag 2009; 13(2):67-75.

Kalb S, Martirosyan LN, Kalani YS, Boc GG, Theodore N. Genetics of the degenerated intervertebral disc. World Neurosurgery 2012; 77(3/4):491-501.

Nong L, Huang Y, Zhao S, Xu N. Vitamin D receptor gene, matrix metalloproteinase 3 polymorphisms and the risk of ıntervertebral disc degeneration susceptibility: meta-analysis. Asian Spine J 2016; 10(5):964-71.

Kalichman L, Hunter DJ. The genetics of intervertebral disc degeneration. Associated genes. Joint Bone Spine 2008; 75:388-96.

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; 84-A(11):2022-8.

Urano T, Narusawa K, Shiraki M, Usui T, Sasaki N, Hosoi T, et al. Association of a single nucleotide polymorphism in the insulin-like growth factor-1 receptor gene with spinal disc degeneration in postmenopausal Japanese women. Spine (Phila Pa 1976) 2008; 33:1256-1.

Dong DM, Yao M, Liu B, Sun CY, Jiang YQ, Wang YS. Association between the -1306C/T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults. Eur Spine J 2007; 16(11):1958-61.

Elmasry S, Asfour S, de Rivero Vaccari JP, Travascio F. Effects of tobacco smoking on the degeneration of the ıntervertebral disc: a finite element study. PLoS One 2015; 10(8):e0136137.

Akmal M, Kesani A, Anand B, Singh A, Wiseman M, Goodship A. Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration. Spine 2004; 29568-75.

Zawilla NH, Darweesh H, Mansour N, Helal S, Taha FM, Awadallah M, et al. Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration. J Occup Rehabil 2014; 24:370-81.

Rajasekaran S, Kanna RM, Reddy RR, Natesan S, Raveendran M, Cheung KM, et al. How Reliable Are the Reported Genetic Associations in Disc Degeneration?: The Influence of Phenotypes, Age, Population Size, and Inclusion Sequence in 809 Patients. Spine (Phila Pa 1976) 2016; 41(21):1649-60.

Carlberg C, Molnar F. Detailed molecular understanding of agonistic and antagonistic vitamin D receptor ligands. Curr Top Med Chem 2006; 6:1243-53.

Cheung KM, Chan D, Karppinen J, Chen Y, Jim JJ, Yip SP, et al. Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population. Spine (Phila Pa 1976) 2006; 31:1143-8.

Mayer JE, Iatridis JC, Chan D, Qureshi SA, Gottesman O, Hecht AC. Genetic polymorphisms associated with intervertebral disc degeneration. Spine J 2013; 13(3): 299-317.

Li Y, Zhu J, Gao C, Peng B. Vitamin D receptor (VDR) genetic polymorphism associated with intervertebral disc degeneration. J Genet Genomics 2015; 42:135-40.

Colombini A, Brayda-Bruno M, Lombardi G, Croiset SJ, Ceriani C, Buligan C, et al. BsmI, ApaI and TaqI Polymorphisms in the vitamin D receptor Gene (VDR) and association with Lumbar spine pathologies: An Italian case-control study. PLoS One 2016; 11(5):e0155004.

Crean JK, Roberts S, Jaffray DC, Eisenstein SM, Duance VC. Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis. Spine (Phila Pa 1976) 1997; 22(24):2877-84.

Weiler C, Nerlich AG, Zipperer J. 2002 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.

Rutges JP, Kummer JA, Oner FC, Verbout AJ, Castelein RJ, Roestenburg HJ, et al. Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels. J Pathol 2008; 214(4):523-30.

Price SJ, Greaves DR, Watkins H. Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem 2001; 276:7549-58.

Martirosyan NL, Patel AA, Carotenuto A, Kalani MY, Belykh E, Walker CT, et al. Genetic Alterations in Intervertebral Disc Disease. Front Surg 2016; 3:59.

Goodrich LR, Hidaka C, Robbins PD, Evans CH, Nixon AJ. Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model. J Bone Joint Surg Br 2007; 89:672-85.

Pattison ST, Melrose J, Ghosh P, Taylor TK. Regulation of gelatinase-A (MMP-2) production by ovine intervertebral disc nukleus pulposus cells grown in alginate bead culture by Transforming Growth Factor-beta(1)and insulin like growth factor-I. Cell Biol Int 2001; 25:679-89.

Nerlich AG, Bachmeier BE, Boos N. Expression of fibronectin and TGF-beta1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue. Eur Spine J 2005; 14:17-26.

Li B, Zheng XF, Ni BB, Yang YH, Jiang SD, Lu H, et al. Reduced expression of insulin-like growth factor 1 receptor leads to accelerated intervertebral disc degeneration in mice. Int J Immunopathol Pharmacol 2013; 26(2):337-47.

Author biographies is not available.