Abstract
Intervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.
References
Annunen, S., Paassilta, P., Lohiniva, J., Perälä, M., Pihlajamaa, T., Karppinen, J., Tervonen, O., Kröger, H., Lähde, S., Vanharanta, H., et al. (1999). An allele of COL9A2 associated with intervertebral disc disease. Science 285, 409–412.10.1126/science.285.5426.409Search in Google Scholar PubMed
Cevei, M., Roşca, E., Liviu, L., Muţiu, G., Stoicanescu, D., and Vasile, L. (2011). Imagistic and histopathologic concordances in degenerative lesions of intervertebral disks. Rom. J. Morphol. Embryol. 52, 327–332.Search in Google Scholar
Cheung, K.M., Chan, D., Karppinen, J., Chen, Y., Jim, J.J., Yip, S.-P., Ott, J., Wong, K.K., Sham, P., Luk, K.D., et al. (2006). Association of the TaqI allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population. Spine 31, 1143–1148.10.1097/01.brs.0000216530.41838.d3Search in Google Scholar PubMed
Cho, H., Park, S.-H., Lee, S., Kang, M., Hasty, K.A., and Kim, S.-J. (2011). Snapshot of degenerative aging of porcine intervertebral disc: a model to unravel the molecular mechanisms. Exp. Mol. Med. 43, 334–340.10.3858/emm.2011.43.6.036Search in Google Scholar PubMed PubMed Central
Dai, F., Belfer, I., Schwartz, C.E., Banco, R., Martha, J.F., Tighioughart, H., Tromanhauser, S.G., Jenis, L.G., and Kim, D.H. (2010). Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. Spine J. 10, 949–957.10.1016/j.spinee.2010.07.387Search in Google Scholar PubMed
Dong, D.M., Yao, M., Liu, B., Sun, C.Y., Jiang, Y.Q., and Wang, Y.S. (2007). Association between the -1306C/ T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults. Eur. Spine J. 16, 1958–1961.10.1007/s00586-007-0454-3Search in Google Scholar PubMed PubMed Central
Eser, O., Eser, B., Cosar, M., Erdogan, M., Aslan, A., Yıldız, H., Solak, M., and Haktanır, A. (2011). Short aggrecan gene repetitive alleles associated with lumbar degenerative disc disease in Turkish patients. Genet. Mol. Res. 10, 1923–1930.10.4238/vol10-3gmr1222Search in Google Scholar PubMed
Eskola, P. (2012). The Search for Susceptibility Genes in Lumbar Disc Degeneration (Oulu, Finland: University of Oulu).Search in Google Scholar
Gennari, L., Becherini, L., Mansani, R., Masi, L., Falchetti, A., Morelli, A., Colli, E., Gonnelli, S., Cepollaro, C., and Brandi, M.L. (1999). FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women. J. Bone Miner. Res. 14, 1379–1386.10.1359/jbmr.1999.14.8.1379Search in Google Scholar PubMed
Gilbert, H.T., Hoyland, J.A., and Millward-Sadler, S.J. (2010). The response of human annulus fibrosus cells to cyclic tensile strain is frequency-dependent and altered with disc degeneration. Arthritis Rheum. 62, 3385–3394.10.1002/art.27643Search in Google Scholar PubMed
Gruber, H.E., Hoelscher, G.L., and Hanley, E.N. (2010). Annulus cells from more degenerated human discs show modified gene expression in 3D culture compared with expression in cells from healthier discs. Spine J. 10, 721–727.10.1016/j.spinee.2010.05.014Search in Google Scholar PubMed
Gruber, H.E., Hoelscher, G.L., Ingram, J.A., Bethea, S., Zinchenko, N., and Hanley, E.N., Jr. (2011). Variations in aggrecan localization and gene expression patterns characterize increasing stages of human intervertebral disk degeneration. Exp. Mol. Pathol. 91, 534–539.10.1016/j.yexmp.2011.06.001Search in Google Scholar PubMed
Gu, J., Guan, F., Guan, G., Xu, G., Wang, X., Zhao, W., Ji, Y., and Yan, J. (2013). Aggrecan variable number of tandem repeat polymorphism and lumbar disc degeneration: a meta-analysis. Spine 38, E1600–E1607.10.1097/BRS.0000000000000012Search in Google Scholar PubMed
Hirose, Y., Chiba, K., Karasugi, T., Nakajima, M., Kawaguchi, Y., Mikami, Y., Furuichi, T., Mio, F., Miyake, A., Miyamoto, T., et al. (2008). A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am. J. Hum. Genet. 82, 1122–1129.10.1016/j.ajhg.2008.03.013Search in Google Scholar PubMed PubMed Central
Huang, Z., Zheng, Z., and Yan, J. (2011). Transgenic expression of human IGF1 in intervertebral degenerative discs. J. Int. Med. Res. 39, 446–455.10.1177/147323001103900212Search in Google Scholar PubMed
Jim, J.J., Noponen-Hietala, N., Cheung, K.M., Ott, J., Karppinen, J., Sahraravand, A., Luk, K.D., Yip, S.P., Sham, P.C., Song, Y.Q., et al. (2005). The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration. Spine 30, 2735–2742.10.1097/01.brs.0000190828.85331.efSearch in Google Scholar PubMed
Kalb, S., Martirosyan, N.L., Kalani, M.Y.S., Broc, G.G., and Theodore, N. (2012). Genetics of the degenerated intervertebral disc. World Neurosurg. 77, 491–501.10.1016/j.wneu.2011.07.014Search in Google Scholar PubMed
Kalichman, L. and Hunter, D.J. (2008). The genetics of intervertebral disc degeneration. Associated genes. Joint Bone Spine 75, 388–396.10.1016/j.jbspin.2007.11.002Search in Google Scholar PubMed
Karppinen, J., Pääkkö, E., Räinä, S., Tervonen, O., Kurunlahti, M., Nieminen, P., Ala-Kokko, L., Malmivaara, A., and Vanharanta, H. (2002). Magnetic resonance imaging findings in relation to the COL9A2 tryptophan allele among patients with sciatica. Spine 27, 78–82.10.1097/00007632-200201010-00018Search in Google Scholar PubMed
Karppinen, J., Solovieva, S., Luoma, K., Raininko, R., Leino-Arjas, P., and Riihimäki, H. (2009). Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men. Eur. Spine J. 18, 1963–1970.10.1007/s00586-009-1139-xSearch in Google Scholar PubMed PubMed Central
Kawaguchi, Y., Osada, R., Kanamori, M., Ishihara, H., Ohmori, K., Matsui, H., and Kimura, T. (1999). Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine 24, 2456.10.1097/00007632-199912010-00006Search in Google Scholar PubMed
Kawaguchi, Y., Kanamori, M., Ishihara, H., Ohmori, K., Matsui, H., and Kimura, T. (2002). The association of lumbar disc disease with vitamin-D receptor gene polymorphism. J. Bone Joint Surg. Am. 84, 2022–2028.10.2106/00004623-200211000-00018Search in Google Scholar PubMed
Kelempisioti, A., Eskola, P.J., Okuloff, A., Karjalainen, U., Takatalo, J., Daavittila, I., Niinimaki, J., Sequeiros, R.B., Tervonen, O., Solovieva. S., et al. (2011). Genetic susceptibility of intervertebral disc degeneration among young Finnish adults. BMC Med. Genet. 12, 153.10.1186/1471-2350-12-153Search in Google Scholar PubMed PubMed Central
Kim, D.H., Dai, F., Belfer, I., Banco, R.J., Martha, J.F., Tighiouart, H., Tromanhauser, S.G., Jenis, L.G., Hunter, D.J., and Schwartz, C.E. (2010). Polymorphic variation of the guanosine triphosphate cyclohydrolase 1 gene predicts outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. Spine 35, 1909–1914.10.1097/BRS.0b013e3181eea007Search in Google Scholar PubMed
Kim, N.K., Shin, D.A., Han, I.B., Yoo, E.H., Kim, S.H., and Chung, S.S. (2011). The association of aggrecan gene polymorphism with the risk of intervertebral disc degeneration. Acta Neurochir. 153, 129–133.10.1007/s00701-010-0831-2Search in Google Scholar PubMed
Lin, W., Lin, J., Chen, X., Wu, C., Zhang, L., Huang, Z., and Lai, J. (2011). Interleukin-10 promoter polymorphisms associated with susceptibility to lumbar disc degeneration in a Chinese cohort. Genet. Mol. Res. 10, 1719–1727.10.4238/vol10-3gmr1283Search in Google Scholar PubMed
Mashayekhi, F., Shafiee, G., Kazemi, M., and Dolati, P. (2010). Lumbar disk degeneration disease and aggrecan gene polymorphism in northern Iran. Biochem. Genet. 48, 684–689.10.1007/s10528-010-9350-3Search in Google Scholar PubMed
Min, S.-K., Nakazato, K., Yamamoto, Y., Gushiken, K., Fujimoto, H., Fujishiro, H., Kobayakawa, Y., and Hiranuma, K. (2010). Cartilage intermediate layer protein gene is associated with lumbar disc degeneration in male, but not female, collegiate athletes. Am. J. Sports Med. 38, 2552–2557.10.1177/0363546510376714Search in Google Scholar PubMed
Noponen-Hietala, N., Virtanen, I., Karttunen, R., Schwenke, S., Jakkula, E., Li, H., Merikivi, R., Barral, S., Ott, J., Karppinen, J., et al. (2005). Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica. Pain 114, 186–194.10.1016/j.pain.2004.12.015Search in Google Scholar PubMed
Omair, A., Lie, B.A., Reikeras, O., Holden, M., and Brox, J.I. (2012). Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic association study. BMC Musculoskelet. Disord. 13, 76.10.1186/1471-2474-13-76Search in Google Scholar PubMed PubMed Central
Paassilta, P., Lohiniva, J., Göring, H.H., Perälä, M., Räinä, S.S., Karppinen, J., Hakala, M., Palm, T., Kröger, H., Kaitila, I., et al. (2001). Identification of a novel common genetic risk factor for lumbar disk disease. J. Am. Med. Assoc. 285, 1843–1849.10.1001/jama.285.14.1843Search in Google Scholar PubMed
Park, J.Y., Kuh, S.U., Park, H.S., and Kim, K.S. (2011). Comparative expression of matrix-associated genes and inflammatory cytokines-associated genes according to disc degeneration: analysis of living human nucleus pulposus. J. Spinal Disord. Tech. 24, 352–357.10.1097/BSD.0b013e3181fee4dfSearch in Google Scholar PubMed
Patel, A.A., Spiker, W.R., Daubs, M., Brodke, D., and Cannon-Albright, L.A. (2011). Evidence for an inherited predisposition to lumbar disc disease. J. Bone Joint Surg. Am. 93, 225–229.10.2106/JBJS.J.00276Search in Google Scholar PubMed PubMed Central
Pluijm, S.M., van Essen, H.W., Bravenboer, N., Uitterlinden, A.G., Smit, J.H., Pols, H.A., and Lips, P. (2004). Collagen type I α1 Sp1 polymorphism, osteoporosis, and intervertebral disc degeneration in older men and women. Ann. Rheum. Dis. 63, 71–77.10.1136/ard.2002.002287Search in Google Scholar PubMed PubMed Central
Roughley, P., Martens, D., Rantakokko, J., Alini, M., Mwale, F., and Antoniou, J. (2006). The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage. Eur. Cell. Mater. 11, 1–7.10.22203/eCM.v011a01Search in Google Scholar
Rut, M., Machoy-Mokrzyńska, A., Ręcławowicz, D., Słoniewski, P., Kurzawski, M., Droździk, M., Safranow, K., Morawska, M., and 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. 156, 245–252.10.1007/s00701-013-1895-6Search in Google Scholar PubMed PubMed Central
Sobajima, S., Shimer, A.L., Chadderdon, R.C., Kompel, J.F., Kim, J.S., Gilbertson, L.G., and Kang, J.D. (2005). Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction. Spine J. 5, 14–23.10.1016/j.spinee.2004.05.251Search in Google Scholar PubMed
Solovieva, S., Kouhia, S., Leino-Arjas, P., Ala-Kokko, L., Luoma, K., Raininko, R., Saarela, J., and Riihimaki, H. (2004). Interleukin 1 polymorphisms and intervertebral disc degeneration. Epidemiology 15, 626–633.10.1097/01.ede.0000135179.04563.35Search in Google Scholar PubMed
Tilkeridis, C., Bei, T., Garantziotis, S., and Stratakis, C. (2005). Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits. J. Med. Genet. 42, e44.10.1136/jmg.2005.033225Search in Google Scholar PubMed PubMed Central
Urano, T., Narusawa, K., Shiraki, M., Usui, T., Sasaki, N., Hosoi, T., Ouchi, Y., Nakamura, T., and Inoue, S. (2008). Association of a single nucleotide polymorphism in the insulin-like growth factor-1 receptor gene with spinal disc degeneration in postmenopausal Japanese women. Spine 33, 1256–1261.10.1097/BRS.0b013e3181715304Search in Google Scholar PubMed
Urano, T., Narusawa, K., Kobayashi, S., Shiraki, M., Horie-Inoue, K., Sasaki, N., Hosoi, T., Ouchi, Y., Nakamura, T., and Inoue, S. (2010). Association of HTRA1 promoter polymorphism with spinal disc degeneration in Japanese women. J. Bone Miner. Metab. 28, 220–226.10.1007/s00774-009-0124-0Search in Google Scholar PubMed
Urano, T., Narusawa, K., Shiraki, M., Sasaki, N., Hosoi, T., Ouchi, Y., Nakamura, T., and Inoue, S. (2011). Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women. Eur. Spine J. 20, 572–577.10.1007/s00586-010-1598-0Search in Google Scholar PubMed PubMed Central
Urban, J. and Roberts, S. (2003). Degeneration of the intervertebral disc. Arthritis Res. Ther. 5, 120–130.10.1186/ar629Search in Google Scholar PubMed PubMed Central
Videman, T., Leppävuori, J., Kaprio, J., Battié, M.C., Gibbons, L.E., Peltonen, L., and Koskenvuo, M. (1998). 1998 volvo award winner in basic science studies: intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine 23, 2477–2485.10.1097/00007632-199812010-00002Search in Google Scholar PubMed
Videman, T., Gibbons, L.E., Battié, M.C., Maravilla, K., Vanninen, E., Leppävuori, J., Kaprio, J., and Peltonen, L. (2001). The relative roles of intragenic polymorphisms of the vitamin D receptor gene in lumbar spine degeneration and bone density. Spine 26, A1–A6.10.1097/00007632-200102010-00003Search in Google Scholar PubMed
Videman, T., Saarela, J., Kaprio, J., Näkki, A., Levälahti, E., Gill, K., Peltonen, L., and Battié, M.C. (2009). Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing. Arthritis Rheum. 60, 470–481.10.1002/art.24268Search in Google Scholar PubMed
Wang, Z., Kim, J.H., Higashino, K., Kim, S.S., Wang, S., Seki, S., Hutton, W.C., and Yoon, S.T. (2012). Cartilage intermediate layer protein (CILP) regulation in intervertebral discs: the effect of age, degeneration, and bone morphogenetic protein-2. Spine 37, E203–E208.10.1097/BRS.0b013e31822dcf47Search in Google Scholar PubMed
Williams, F.M. and Sambrook, P.N. (2011). Neck and back pain and intervertebral disc degeneration: role of occupational factors. Best Pract. Res. Clin. Rheumatol. 25, 69–79.10.1016/j.berh.2011.01.007Search in Google Scholar PubMed
Yang, S.H., Lin, C.C., Hu, M.H., Shih, T.T.F., Sun, Y.H., and Lin, F.H. (2010). Influence of age-related degeneration on regenerative potential of human nucleus pulposus cells. J. Orthop. Res. 28, 379–383.10.1002/jor.20988Search in Google Scholar PubMed
Zhang, Y.-G., Guo, X., Sun, Z., Jia, G., Xu, P., and Wang, S. (2010). Gene expression profiles of disc tissues and peripheral blood mononuclear cells from patients with degenerative discs. J. Bone Miner. Metab. 28, 209–219.10.1007/s00774-009-0120-4Search in Google Scholar PubMed
Zhu, Y., Wu, J.-J., Weis, M.A., Mirza, S.K., and Eyre, D.R. (2011). Type IX collagen neo-deposition in degenerative discs of surgical patients whether genotyped plus or minus for COL9 risk alleles. Spine 36, 2031.10.1097/BRS.0b013e3181ffdd61Search in Google Scholar PubMed PubMed Central
©2015 by De Gruyter