Skip to main content
SpringerLink
Log in

Genetic Basis of Intervertebral Disc Degeneration

  • Chapter
  • First Online:
Book cover The Intervertebral Disc

Abstract

Genetics is an area of study that connects genes with functions, variations with phenotypes, and, of most interest to scientists and clinicians, mutations with diseases. According to the Online Mendelian Inheritance in Man (OMIM), an online catalog for human genes and Mendelian disorders, over 3,000 known “genotype-phenotype” pairs have been recorded. A direct application of such knowledge is diagnosis, of which prenatal testing and newborn screening of rare conditions are common nowadays; ideally, this would be extended in future for disease prevention or the development of personalized medicine. It is clear that our understanding of disease mechanism of rare skeletal disorders such as osteogenesis imperfecta (OI), spondyloepiphyseal dysplasia (SED), achondroplasia, and Ehlers-Danlos syndrome (EDS) has come directly from knowing the genes involved, allowing detailed in vitro and in vivo functional studies. While more difficult for common disorders such as intervertebral disc degeneration, the same principle can be applied, bearing in mind the effect size, the number of genes involved, and contributions from environment factors. These are the issues that this chapter will address systematically, namely, to provide the basic concepts of what genetic studies can achieve and with the benefit of hindsight from studies of similar disorders such as osteoarthritis (OA) to generate a road map for studies of intervertebral disc degeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 1000 Genomes Project Consortium GP (2010) A map of human genome variation from population-scale sequencing. Nature 467(7319):1061–1073

    Article  CAS  Google Scholar 

  • Aladin DM, Cheung KM et al (2007) Expression of the Trp2 allele of COL9A2 is associated with alterations in the mechanical properties of human intervertebral discs. Spine 32(25):2820–2826

    Article  PubMed  Google Scholar 

  • Alanay Y, Avaygan H et al (2010) Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 86(4):551–559

    Article  PubMed  CAS  Google Scholar 

  • Altshuler DM, Gibbs RA et al (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467(7311):52–58

    Article  PubMed  CAS  Google Scholar 

  • Annunen S, Paassilta P et al (1999) An allele of COL9A2 associated with intervertebral disc disease. Science 285(5426):409–412

    Article  PubMed  CAS  Google Scholar 

  • Barnes AM, Chang W et al (2006) Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. N Engl J Med 355(26):2757–2764

    Article  PubMed  CAS  Google Scholar 

  • Battie MC, Haynor DR et al (1995a) Similarities in degenerative findings on magnetic resonance images of the lumbar spines of identical twins. J Bone Joint Surg Am 77(11):1662–1670

    PubMed  CAS  Google Scholar 

  • Battie MC, Videman T et al (1995b) 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(24):2601–2612

    Article  PubMed  CAS  Google Scholar 

  • Bell CG, Finer S et al (2010) Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus. PLoS One 5(11):e14040

    Article  PubMed  CAS  Google Scholar 

  • Benneker LM, Heini PF et al (2005) Correlation of radiographic and MRI parameters to morphological and biochemical assessment of intervertebral disc degeneration. Eur Spine J 14(1):27–35

    Article  PubMed  Google Scholar 

  • Bertram L, Lill CM et al (2010) The genetics of Alzheimer disease: back to the future. Neuron 68(2):270–281

    Article  PubMed  CAS  Google Scholar 

  • Bjornsson HT, Fallin MD et al (2004) An integrated epigenetic and genetic approach to common human disease. Trends Genet 20(8):350–358

    Article  PubMed  CAS  Google Scholar 

  • Bodmer W, Bonilla C (2008) Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 40(6):695–701

    Article  PubMed  CAS  Google Scholar 

  • Bonnefond A, Clement N et al (2012) Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet 44(3):297–301

    Article  PubMed  CAS  Google Scholar 

  • Bornstein P, Agah A et al (2004) The role of thrombospondins 1 and 2 in the regulation of cell-matrix interactions, collagen fibril formation, and the response to injury. Int J Biochem Cell Biol 36(6):1115–1125

    Article  PubMed  CAS  Google Scholar 

  • Boyd LM, Richardson WJ et al (2008) Early-onset degeneration of the intervertebral disc and vertebral end plate in mice deficient in type IX collagen. Arthritis Rheum 58(1):164–171

    Article  PubMed  CAS  Google Scholar 

  • Brest P, Lapaquette P et al (2011) A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn’s disease. Nat Genet 43(3):242–245

    Article  PubMed  CAS  Google Scholar 

  • Cabral WA, Chang W et al (2007) Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet 39(3):359–365

    Article  PubMed  CAS  Google Scholar 

  • Chanock SJ, Manolio T et al (2007) Replicating genotype-phenotype associations. Nature 447(7145):655–660

    Article  PubMed  CAS  Google Scholar 

  • Cheung KM, Chan D et al (2006) Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population. Spine 31(10):1143–1148

    Article  PubMed  Google Scholar 

  • Cheung KM, Karppinen J et al (2009) Prevalence and pattern of lumbar MRI changes in a population study of 1043 individuals. Spine 34(9):934–940

    Article  PubMed  Google Scholar 

  • Cirulli ET, Goldstein DB (2010) Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 11(6):415–425

    Article  PubMed  CAS  Google Scholar 

  • Cong L, Pang H et al (2010a) The interaction between aggrecan gene VNTR polymorphism and cigarette smoking in predicting incident symptomatic intervertebral disc degeneration. Connect Tissue Res 51(5):397–403

    Article  PubMed  CAS  Google Scholar 

  • Cong L, Pang H et al (2010b) Association between the expression of aggrecan and the distribution of aggrecan gene variable number of tandem repeats with symptomatic lumbar disc herniation in Chinese Han of Northern China. Spine 35(14):1371–1376

    PubMed  Google Scholar 

  • Daly MJ (2009) Assessing significance in genetic association studies. Cold Spring Harb Protoc 2009(8):pdb top58

    Article  PubMed  Google Scholar 

  • Davey JW, Hohenlohe PA et al (2011) Genome-wide genetic marker discovery and genotyping using next-generation sequencing. Nat Rev Genet 12(7):499–510

    Article  PubMed  CAS  Google Scholar 

  • Dempster EL, Pidsley R et al (2011) Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet 20(24):4786–4796

    Article  PubMed  CAS  Google Scholar 

  • Doege KJ, Coulter SN et al (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(21):13974–13979

    Article  PubMed  CAS  Google Scholar 

  • Dong DM, Yao M et al (2007) Association between the -1306C/T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults. Eur Spine J 16(11):1958–1961

    Article  PubMed  CAS  Google Scholar 

  • Eichler EE, Flint J et al (2010) Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet 11(6):446–450

    Article  PubMed  CAS  Google Scholar 

  • Eser O, Eser B et al (2011) Short aggrecan gene repetitive alleles associated with lumbar degenerative disc disease in Turkish patients. Genet Mol Res 10(3):1923–1930

    Article  PubMed  CAS  Google Scholar 

  • Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447(7143):433–440

    Article  PubMed  CAS  Google Scholar 

  • Francis-West PH, Abdelfattah A et al (1999) Mechanisms of GDF-5 action during skeletal development. Development 126(6):1305–1315

    PubMed  CAS  Google Scholar 

  • Garnero P, Borel O et al (1998) Collagen Ialpha1 Sp1 polymorphism, bone mass, and bone turnover in healthy French premenopausal women: the OFELY study. J Bone Miner Res 13(5):813–817

    Article  PubMed  CAS  Google Scholar 

  • Goupille P, Jayson MI et al (1998) Matrix metalloproteinases: the clue to intervertebral disc degeneration? Spine 23(14):1612–1626

    Article  PubMed  CAS  Google Scholar 

  • Grant SF, Reid DM et al (1996) Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 14(2):203–205

    Article  PubMed  CAS  Google Scholar 

  • Gruber HE, Ingram JA et al (2009) Asporin, a susceptibility gene in osteoarthritis, is expressed at higher levels in the more degenerate human intervertebral disc. Arthritis Res Ther 11(2):R47

    Article  PubMed  CAS  Google Scholar 

  • Higashino K, Matsui Y et al (2007) The alpha2 type IX collagen tryptophan polymorphism is associated with the severity of disc degeneration in younger patients with herniated nucleus pulposus of the lumbar spine. Int Orthop 31(1):107–111

    Article  PubMed  CAS  Google Scholar 

  • Hindorff LA, MacArthur J et al (2012) A catalog of published genome-wide association studies. Available at www.genome.gov/gwastudies. Accessed 24 Feb 2012

  • Hirose Y, Chiba K 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(5):1122–1129

    Article  PubMed  CAS  Google Scholar 

  • Internation HapMap Consortium (2003) The International HapMap Project. Nature 426(6968):789–796

    Article  CAS  Google Scholar 

  • Ioannidis JP, Boffetta P et al (2008) Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol 37(1):120–132

    Article  PubMed  Google Scholar 

  • Jim JJ, Noponen-Hietala N 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(24):2735–2742

    Article  PubMed  Google Scholar 

  • Jones SW, Watkins G et al (2009) The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13. Osteoarthritis Cartilage 17(4):464–472

    Article  PubMed  CAS  Google Scholar 

  • Kales SN, Linos A et al (2004) The role of collagen IX tryptophan polymorphisms in symptomatic intervertebral disc disease in Southern European patients. Spine 29(11):1266–1270

    Article  PubMed  Google Scholar 

  • Karasugi T, Semba K et al (2009) Association of the tag SNPs in the human SKT gene (KIAA1217) with lumbar disc herniation. J Bone Miner Res 24(9):1537–1543

    Article  PubMed  CAS  Google Scholar 

  • Kawaguchi Y, Osada R et al (1999) Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine 24(23):2456–2460

    Article  PubMed  CAS  Google Scholar 

  • Kawaguchi Y, Kanamori M et al (2002) The association of lumbar disc disease with vitamin-D receptor gene polymorphism. J Bone Joint Surg Am 84-A(11):2022–2028

    PubMed  Google Scholar 

  • Kelempisioti A, Eskola PJ et al (2011) Genetic susceptibility of intervertebral disc degeneration among young Finnish adults. BMC Med Genet 12(1):153

    Article  PubMed  CAS  Google Scholar 

  • Kellgren JH, Jeffrey MR et al (1963) The epidemiology of chronic rheumatism: atlas of standard radiographs. Blackwell Scientific, Oxford

    Google Scholar 

  • Kerkhof HJ, Lories RJ et al (2010) A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22. Arthritis Rheum 62(2):499–510

    PubMed  CAS  Google Scholar 

  • Khoschnau S, Melhus H et al (2008) Type I collagen alpha1 Sp1 polymorphism and the risk of cruciate ligament ruptures or shoulder dislocations. Am J Sports Med 36(12):2432–2436

    Article  PubMed  Google Scholar 

  • Kim NK, Shin DA et al (2011) The association of aggrecan gene polymorphism with the risk of intervertebral disc degeneration. Acta Neurochir (Wien) 153(1):129–133

    Article  Google Scholar 

  • Kimura T, Nakata K et al (1996) Progressive degeneration of articular cartilage and intervertebral discs. An experimental study in transgenic mice bearing a type IX collagen mutation. Int Orthop 20(3):177–181

    Article  PubMed  Google Scholar 

  • Kizawa H, Kou I et al (2005) An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet 37(2):138–144

    Article  PubMed  CAS  Google Scholar 

  • Klatt AR, Klinger G et al (2009) Matrilin-3 activates the expression of osteoarthritis-associated genes in primary human chondrocytes. FEBS Lett 583(22):3611–3617

    Article  PubMed  CAS  Google Scholar 

  • Klatt AR, Becker AK et al (2011) The matrilins: modulators of extracellular matrix assembly. Int J Biochem Cell Biol 43(3):320–330

    Article  PubMed  CAS  Google Scholar 

  • Lapunzina P, Aglan M et al (2010) Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta. Am J Hum Genet 87(1):110–114

    Article  PubMed  CAS  Google Scholar 

  • Le Maitre CL, Freemont AJ et al (2004) Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol 204(1):47–54

    Article  PubMed  CAS  Google Scholar 

  • Le Maitre CL, Freemont AJ et al (2005) The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther 7(4):R732–R745

    Article  PubMed  CAS  Google Scholar 

  • Le Maitre CL, Hoyland JA et al (2007) Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile. Arthritis Res Ther 9(4):R77

    Article  PubMed  CAS  Google Scholar 

  • Lian K, Zmuda JM et al (2005) Type I collagen alpha1 Sp1 transcription factor binding site polymorphism is associated with reduced risk of hip osteoarthritis defined by severe joint space narrowing in elderly women. Arthritis Rheum 52(5):1431–1436

    Article  PubMed  CAS  Google Scholar 

  • Lin WP, Lin JH et al (2011) Interleukin-10 promoter polymorphisms associated with susceptibility to lumbar disc degeneration in a Chinese cohort. Genet Mol Res 10(3):1719–1727

    Article  PubMed  CAS  Google Scholar 

  • Lorenzo P, Bayliss MT et al (1998) A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age. J Biol Chem 273(36):23463–23468

    Article  PubMed  CAS  Google Scholar 

  • Lorenzo P, Aspberg A et al (2001) Identification and characterization of asporin. A novel member of the leucine-rich repeat protein family closely related to decorin and biglycan. J Biol Chem 276(15):12201–12211

    Article  PubMed  CAS  Google Scholar 

  • Loughlin J (2011) Osteoarthritis year 2010 in review: genetics. Osteoarthritis Cartilage 19(4):342–345

    Article  PubMed  CAS  Google Scholar 

  • Mann V, Hobson EE et al (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107(7):899–907

    Article  PubMed  CAS  Google Scholar 

  • Manolio TA, Collins FS et al (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753

    Article  PubMed  CAS  Google Scholar 

  • Marinelli NL, Haughton VM et al (2009) T2 relaxation times of intervertebral disc tissue correlated with water content and proteoglycan content. Spine 34(5):520–524

    Article  PubMed  Google Scholar 

  • Martinez-Glez V, Valencia M et al (2011) Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta. Hum Mutat 33(2):343–350

    Article  PubMed  CAS  Google Scholar 

  • Matsui Y, Wu JJ et al (2003) Matrix deposition of tryptophan-containing allelic variants of type IX collagen in developing human cartilage. Matrix Biol 22(2):123–129

    Article  PubMed  CAS  Google Scholar 

  • Metzker ML (2010) Sequencing technologies – the next generation. Nat Rev Genet 11(1):31–46

    Article  PubMed  CAS  Google Scholar 

  • Millward-Sadler SJ, Costello PW et al (2009) Regulation of catabolic gene expression in normal and degenerate human intervertebral disc cells: implications for the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther 11(3):R65

    Article  PubMed  CAS  Google Scholar 

  • Min JL, Meulenbelt I et al (2006) Association of matrilin-3 polymorphisms with spinal disc degeneration and osteoarthritis of the first carpometacarpal joint of the hand. Ann Rheum Dis 65(8):1060–1066

    Article  PubMed  CAS  Google Scholar 

  • Min SK, Nakazato K et al (2010) Cartilage intermediate layer protein gene is associated with lumbar disc degeneration in male, but not female, collegiate athletes. Am J Sports Med 38(12):2552–2557

    Article  PubMed  Google Scholar 

  • Mio F, Chiba K et al (2007) A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation. Am J Hum Genet 81(6):1271–1277

    Article  PubMed  CAS  Google Scholar 

  • Mitchell BD, Yerges-Armstrong LM (2011) The genetics of bone loss: challenges and prospects. J Clin Endocrinol Metab 96(5):1258–1268

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto Y, Mabuchi A et al (2007) A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet 39(4):529–533

    Article  PubMed  CAS  Google Scholar 

  • Moreau MP, Bruse SE et al (2011) Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder. Biol Psychiatry 69(2):188–193

    Article  PubMed  CAS  Google Scholar 

  • Morello R, Bertin TK et al (2006) CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 127(2):291–304

    Article  PubMed  CAS  Google Scholar 

  • Nakajima M, Takahashi A et al (2010) New sequence variants in HLA class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study. PLoS One 5(3):e9723

    Article  PubMed  CAS  Google Scholar 

  • Nakaoka H, Inoue I (2009) Meta-analysis of genetic association studies: methodologies, between-study heterogeneity and winner’s curse. J Hum Genet 54(11):615–623

    Article  PubMed  Google Scholar 

  • Neale BM, Sham PC (2004) The future of association studies: gene-based analysis and replication. Am J Hum Genet 75(3):353–362

    Article  PubMed  CAS  Google Scholar 

  • Nejentsev S, Walker N et al (2009) Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324(5925):387–389

    Article  PubMed  CAS  Google Scholar 

  • Paassilta P, Lohiniva J et al (2001) Identification of a novel common genetic risk factor for lumbar disk disease. JAMA 285(14):1843–1849

    Article  PubMed  CAS  Google Scholar 

  • Panoutsopoulou K, Southam L et al (2011) Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study. Ann Rheum Dis 70(5):864–867

    Article  PubMed  CAS  Google Scholar 

  • Perkins DO, Jeffries CD et al (2007) microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 8(2):R27

    Article  PubMed  CAS  Google Scholar 

  • Petronis A (2010) Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature 465(7299):721–727

    Article  PubMed  CAS  Google Scholar 

  • Pfirrmann CW, Metzdorf A et al (2001) Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 26(17):1873–1878

    Article  PubMed  CAS  Google Scholar 

  • Pluijm SM, van Essen HW et al (2004) Collagen type I alpha1 Sp1 polymorphism, osteoporosis, and intervertebral disc degeneration in older men and women. Ann Rheum Dis 63(1):71–77

    Article  PubMed  CAS  Google Scholar 

  • Price SJ, Greaves DR et al (2001) Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem 276(10):7549–7558

    Article  PubMed  CAS  Google Scholar 

  • Rakyan VK, Beyan H et al (2011a) Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet 7(9):e1002300

    Article  PubMed  CAS  Google Scholar 

  • Rakyan VK, Down TA et al (2011b) Epigenome-wide association studies for common human diseases. Nat Rev Genet 12(8):529–541

    Article  PubMed  CAS  Google Scholar 

  • Ripke S, Sanders AR et al (2011) Genome-wide association study identifies five new schizophrenia loci. Nat Genet 43(10):969–976

    Article  CAS  Google Scholar 

  • Roberts S, Caterson B et al (2000) Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc. Spine 25(23):3005–3013

    Article  PubMed  CAS  Google Scholar 

  • Sambrook PN, MacGregor AJ et al (1999) Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 42(2):366–372

    Article  PubMed  CAS  Google Scholar 

  • Schneiderman G, Flannigan B et al (1987) Magnetic resonance imaging in the diagnosis of disc degeneration: correlation with discography. Spine 12(3):276–281

    Article  PubMed  CAS  Google Scholar 

  • Seki S, Kawaguchi Y et al (2005) A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet 37(6):607–612

    Article  PubMed  CAS  Google Scholar 

  • Seki S, Kawaguchi Y et al (2006) Association study of COL9A2 with lumbar disc disease in the Japanese population. J Hum Genet 51(12):1063–1067

    Article  PubMed  CAS  Google Scholar 

  • Semba K, Araki K et al (2006) A novel murine gene, Sickle tail, linked to the Danforth’s short tail locus, is required for normal development of the intervertebral disc. Genetics 172(1):445–456

    Article  PubMed  CAS  Google Scholar 

  • Sethupathy P, Borel C et al (2007) Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3′ untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet 81(2):405–413

    Article  PubMed  CAS  Google Scholar 

  • Skorupski P, Krol J et al (2006) An alpha-1 chain of type I collagen Sp1-binding site polymorphism in women suffering from stress urinary incontinence. Am J Obstet Gynecol 194(2):346–350

    Article  PubMed  CAS  Google Scholar 

  • So HC, Gui AH et al (2011) Evaluating the heritability explained by known susceptibility variants: a survey of ten complex diseases. Genet Epidemiol 35(5):310–317

    Article  PubMed  Google Scholar 

  • Solovieva S, Lohiniva J et al (2002) COL9A3 gene polymorphism and obesity in intervertebral disc degeneration of the lumbar spine: evidence of gene-environment interaction. Spine 27(23):2691–2696

    Article  PubMed  Google Scholar 

  • Solovieva S, Kouhia S et al (2004) Interleukin 1 polymorphisms and intervertebral disc degeneration. Epidemiology 15(5):626–633

    Article  PubMed  Google Scholar 

  • Solovieva S, Lohiniva J et al (2006) Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms. Eur Spine J 15(5):613–619

    Article  PubMed  Google Scholar 

  • Solovieva S, Noponen N et al (2007) Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration. Spine 32(16):1700–1705

    Article  PubMed  Google Scholar 

  • Song YQ, Cheung KM et al (2008a) Association of the asporin D14 allele with lumbar-disc degeneration in Asians. Am J Hum Genet 82(3):744–747

    Article  PubMed  CAS  Google Scholar 

  • Song YQ, Ho DW et al (2008b) Association between promoter -1607 polymorphism of MMP1 and lumbar disc disease in Southern Chinese. BMC Med Genet 9:38

    Article  PubMed  CAS  Google Scholar 

  • Speer G, Szenthe P et al (2006) Myocardial infarction is associated with Spl binding site polymorphism of collagen type 1A1 gene. Acta Cardiol 61(3):321–325

    Article  PubMed  Google Scholar 

  • Stefansson H, Rujescu D et al (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455(7210):232–236

    Article  PubMed  CAS  Google Scholar 

  • Sun ZM, Miao L et al (2009) Association between the -1562 C/T polymorphism of matrix metalloproteinase-9 gene and lumbar disc disease in the young adult population in North China. Connect Tissue Res 50(3):181–185

    Article  PubMed  CAS  Google Scholar 

  • Tabor HK, Risch NJ et al (2002) Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 3(5):391–397

    Article  PubMed  CAS  Google Scholar 

  • Takahashi M, Haro H et al (2001) 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 83(4):491–495

    Article  PubMed  CAS  Google Scholar 

  • Tilkeridis C, Bei T et al (2005) Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits. J Med Genet 42(7):e44

    Article  PubMed  CAS  Google Scholar 

  • Uitterlinden AG, Burger H et al (1998) Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med 338(15):1016–1021

    Article  PubMed  CAS  Google Scholar 

  • Uitterlinden AG, Fang Y et al (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338(2):143–156

    Article  PubMed  CAS  Google Scholar 

  • Urano T, Narusawa K et al (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(11):1256–1261

    Article  PubMed  Google Scholar 

  • Valdes AM, Spector TD (2011) Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol 7(1):23–32

    Article  PubMed  Google Scholar 

  • Valdes AM, Hassett G et al (2005) Radiographic progression of lumbar spine disc degeneration is influenced by variation at inflammatory genes: a candidate SNP association study in the Chingford cohort. Spine 30(21):2445–2451

    Article  PubMed  Google Scholar 

  • van Dijk FS, Nesbitt IM et al (2009) PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet 85(4):521–527

    Article  PubMed  CAS  Google Scholar 

  • Videman T, Nummi P et al (1994) Digital assessment of MRI for lumbar disc desiccation. A comparison of digital versus subjective assessments and digital intensity profiles versus discogram and macroanatomic findings. Spine 19(2):192–198

    Article  PubMed  CAS  Google Scholar 

  • Videman T, Leppavuori J et al (1998) Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine 23(23):2477–2485

    Article  PubMed  CAS  Google Scholar 

  • Videman T, Saarela J et al (2009) Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing. Arthritis Rheum 60(2):470–481

    Article  PubMed  CAS  Google Scholar 

  • Vikkula M, Palotie A et al (1993) Early-onset osteoarthritis linked to the type II procollagen gene. Detailed clinical phenotype and further analyses of the gene. Arthritis Rheum 36(3):401–409

    Article  PubMed  CAS  Google Scholar 

  • Virtanen IM, Song YQ et al (2007) Phenotypic and population differences in the association between CILP and lumbar disc disease. J Med Genet 44(4):285–288

    Article  PubMed  CAS  Google Scholar 

  • Visscher PM, Hill WG et al (2008) Heritability in the genomics era – concepts and misconceptions. Nat Rev Genet 9(4):255–266

    Article  PubMed  CAS  Google Scholar 

  • Visscher PM, Brown MA et al (2012) Five years of GWAS discovery. Am J Hum Genet 90(1):7–24

    Article  PubMed  CAS  Google Scholar 

  • Wagner GP, Zhang J (2011) The pleiotropic structure of the genotype-phenotype map: the evolvability of complex organisms. Nat Rev Genet 12(3):204–213

    Article  PubMed  CAS  Google Scholar 

  • Williams FM, Popham M et al (2011) GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women. Arthritis Rheum 63(3):708–712

    Article  PubMed  CAS  Google Scholar 

  • Wrocklage C, Wassmann H et al (2000) COL9A2 allelotypes in intervertebral disc disease. Biochem Biophys Res Commun 279(2):398–400

    Article  PubMed  CAS  Google Scholar 

  • Zeller T, Blankenberg S et al (2012) Genomewide association studies in cardiovascular disease – an update 2011. Clin Chem 58(1):92–103

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work is supported by the University Grants Committee of Hong Kong (AoE/M-04/04) and AOSPINE (AOSBRC-07-2).

Author information

Authors and Affiliations

  1. Department of Biochemistry, The University of Hong Kong, 3/F Laboratory Block, LKS Faculty of Medicine, 21 Sassoon Road, Pokfulam, Hong Kong

    Anita Yee & Danny Chan

Authors
  1. Anita Yee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Danny Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Danny Chan .

Editor information

Editors and Affiliations

  1. Jefferson Medical College Div Ortho Rsch/Dept Othro Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Irving M. Shapiro

  2. Jefferson Medical College Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Makarand V. Risbud

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Wien

About this chapter

Cite this chapter

Yee, A., Chan, D. (2014). Genetic Basis of Intervertebral Disc Degeneration. In: Shapiro, I., Risbud, M. (eds) The Intervertebral Disc. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1535-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-1535-0_10

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-1534-3

  • Online ISBN: 978-3-7091-1535-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation