Abstract
Background
Intervertebral disc degeneration is now considered to be genetically determined in large part, with environmental factors also playing an important role. The human is known to uniquely exhibit variable numbers of tandem repeat polymorphism within the aggrecan CS1 domain. To date, the analysis of aggrecan’s variable numbers of tandem repeat polymorphism has given inconsistent results with respect to the correlation between the allele’s size and intervertebral disc degeneration. We wanted to investigate the patterns of the variable numbers of tandem repeat polymorphism in the aggrecan CS1 domain of Koreans, and we analyzed the association between the polymorphism and intervertebral disc degeneration.
Method
A total of 66 males and 38 females participated in this study. Their ages ranged from 13 to 73 years. Genomic deoxyribonucleic acid was extracted from blood samples and PCR was carried out to detect the alleles of the aggrecan gene. The subjects were evaluated on MRI and they were classified by the number, severity, and morphology of disc degeneration.
Findings
The genotyping identified 11 alleles ranging from 21 to 36 repeats. Alleles 13, 18, 19, and 20 were not found in this study. Of the 104 subjects, 29 (28%) were homozygotes and 75 (72%) were heterozygotes. Allele 27 (39%) was the most common form together with alleles 26 (26%) and 28 (14%). The allele 36 is the longest among the alleles ever discovered. For the case that the analysis was limited to subjects with the fourth decades or less, the 21 allele was significantly overrepresented among the persons with multilevel disc degeneration (p < 0.006).
Conclusions
Carrying a copy of the allele with 21 repeats might increase the risk of multiple disc degeneration in the subjects below the age of 40 years.
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References
Adams MA, Freeman BJ, Morrison HP, Nelson IW, Dolan P (2000) Mechanical initiation of intervertebral disc degeneration. Spine (Phila Pa 1976) 25:1625–1636
Andersson GB (1998) Epidemiology of low back pain. Acta Orthop Scand Suppl 281:28–31
Ala-Kokko L (2002) Genetic risk factors for lumbar disc disease. Ann Med 34:42–47
Battie MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K (1995) 1995 Volvo Award in clinical sciences. Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine 20:2601–2612
Heikkila JK, Koskenvuo M, Heliovaara M, Kurppa K, Riihimaki H, Heikkila K, Rita H, Videman T (1989) Genetic and environmental factors in sciatica. Evidence from a nationwide panel of 9365 adult twin pairs. Ann Med 21:393–398
Sambrook PN, MacGregor AJ, Spector TD (1999) Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 42:366–372
Videman T, Battie MC, Ripatti S, Gill K, Manninen H, Kaprio J (2006) Determinants of the progression in lumbar degeneration: a 5-year follow-up study of adult male monozygotic twins. Spine (Phila Pa 1976) 31:671–678
Battie MC, Videman T, Kaprio J, Gibbons LE, Gill K, Manninen H, Saarela J, Peltonen L (2009) The twin spine study: contributions to a changing view of disc degeneration. Spine J 9:47–59
Bull J, el Gammal T, Popham M (1969) A possible genetic factor in cervical spondylosis. Br J Radiol 42:9–16
Kalichman L, Hunter DJ (2008) The genetics of intervertebral disc degeneration. Associated genes. Joint Bone Spine 75:388–396
Videman T, Saarela J, Kaprio J, Nakki A, Levalahti E, Gill K, Peltonen L, Battie MC (2009) Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing. Arthritis Rheum 60:470–481
Pearce RH, Grimmer BJ, Adams ME (1987) Degeneration and the chemical composition of the human lumbar intervertebral disc. J Orthop Res 5:198–205
Roughley PJ, Alini M, Antoniou J (2002) The role of proteoglycans in aging, degeneration and repair of the intervertebral disc. Biochem Soc Trans 30:869–874
Watanabe H, Yamada Y, Kimata K (1998) Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. J Biochem 124:687–693
Doege KJ, Coulter SN, Meek LM, Maslen K, Wood JG (1997) A human-specific polymorphism in the coding region of the aggrecan gene. Variable number of tandem repeats produce a range of core protein sizes in the general population. J Biol Chem 272:13974–13979
Kawaguchi Y, Osada R, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T (1999) Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine 24:2456–2460
Roughley P, Martens D, Rantakokko J, Alini M, Mwale F, Antoniou J (2006) The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage. Eur Cell Mater 11:1–7, discussion 7
Luoma K, Raininko R, Nummi P, Luukkonen R (1993) Is the signal intensity of cerebrospinal fluid constant? Intensity measurements with high and low field magnetic resonance imagers. Magn Reson Imaging 11:549–555
Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N (2001) Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 26:1873–1878
Fardon DF, Milette PC (2001) Nomenclature and classification of lumbar disc pathology. Recommendations of the combined task forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Spine (Phila Pa 1976) 26:E93–E113
Doege KJ, Sasaki M, Kimura T, Yamada Y (1991) Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms. J Biol Chem 266:894–902
Tortorella MD, Malfait AM, Deccico C, Arner E (2001) The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation. Osteoarthritis Cartilage 9:539–552
Solovieva S, Noponen N, Mannikko M, Leino-Arjas P, Luoma K, Raininko R, Ala-Kokko L, Riihimaki H (2007) Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration. Spine 32:1700–1705
Horton WE Jr, Lethbridge-Cejku M, Hochberg MC, Balakir R, Precht P, Plato CC, Tobin JD, Meek L, Doege K (1998) An association between an aggrecan polymorphic allele and bilateral hand osteoarthritis in elderly white men: data from the Baltimore Longitudinal Study of Aging (BLSA). Osteoarthritis Cartilage 6:245–251
Roughley PJ, Melching LI, Heathfield TF, Pearce RH, Mort JS (2006) The structure and degradation of aggrecan in human intervertebral disc. Eur Spine J 15(Suppl 3):S326–S332
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Kim, N.K., Shin, D.A., Han, I.B. et al. The association of aggrecan gene polymorphism with the risk of intervertebral disc degeneration. Acta Neurochir 153, 129–133 (2011). https://doi.org/10.1007/s00701-010-0831-2
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DOI: https://doi.org/10.1007/s00701-010-0831-2