Skip to main content
  • Association of COL1A1 Sp1 Gene Polymorphism with Degenerated Intervertebral Disc Prolapse from a Subset of Indian Population: A Case Control Study

    Final Number:

    Shailendra Deepak Anjankar MBBS; Subodh Raju

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2015 Annual Meeting

    Introduction: Degenerated Disc Disease (DDD) is a very common disorder responsible for increased morbidity in productive age group. Its etiology is multifactorial and genetic factors have been predominantly implicated. Disc prolapse results due to tear in annulus, which is a fibrous structure composed largely of type I Collagen. Functional polymorphism at the Sp1 site of the COL1A1 (Collagen I alpha 1) gene has shown positive association with DDD in Dutch and Greek populations.

    Methods: 50 clinically and radiologically proven patients of disc prolapse requiring surgery were included as cases and 50 healthy, age matched volunteers served as controls. After isolating DNA from their blood sample, genotyping for COL1A1 polymorphism (rs1800012) was performed and identified as GG, GT and TT.

    Results: The mean age and body mass index in cases and controls were similar. 76% of the patients were males. Commonest site of disc degeneration was L4-5 (36%), followed by L5-S1 (34%). Homozygous – GG, heterozygous GT and homozygous TT genotypes were seen in 38(76%), 10 (20%) and 2(4%) cases respectively, controls had similar percentage of the genotypes as well. The alleles in cases and control group showed no significant difference (p=0.6744) and followed the Hardy-Weinberg Equilibrium in the study population.

    Conclusions: The COL1A1 (rs1800012) is in Hardy Weinberg equilibrium in the present subset of Indian population. But taken as a single factor, it was not found to be associated with DDD in this preliminary study. Disc degeneration is multifactorial and also anticipated to be a result of multiple genes involvement and gene – gene interaction.

    Patient Care: Such studies will help to guide research in future, to identify the genes involved in disc prolapse, and develop molecular medicine to alter the expression of genes for development of normal anatomical morphological structure of human body. And also help in identifying the individuals who are prone for disc prolapse, so that precautions and life style modifications may suggested.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Identify the gene which is responsible for defective development of Collagen 1 which can cause disc prolapse. 2) Understand the fact that multiple genes, gene - gene interaction, gene - environment interaction may be the reason for disc prolapse

    References: Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999;354:581-5. Maniadakis N, Gray A. The economic burden of back pain in UK. Pain 2000;84:95-103. Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976) 2006;31:2151-61. Heikkilä JK, Koskenvuo M, Heliövaara M, Kurppa K, Riihimäki H, Heikkilä K, et al. Genetic and environmental factors in sciatica. Evidence from a nationwide panel of 9365 adult twin pairs. Ann Med 1989;21:393-8. Okada E, Matsumoto M, Fujiwara H, Toyama Y. Disc degeneration of cervical spine on MRI in patients with lumbar disc herniation: comparison study with asymptomatic volunteers. Eur Spine J 2011;20:585-91. Kraemer J. History and terminology. Intervertebral Disk Diseases – Causes, Diagnosis, Treatment and Prophylaxis. 3rd ed., Ch. 2. New York: Thieme Medical and Scientific Publishers Private Ltd.; 2010. p. 12. Ala-Kokko L. Genetic risk factors for lumbar disc disease. Ann Med 2002;34:42-7. Battié MC, Videman T, Levalahti E, Gill K, Kaprio J. Heritability of low back pain and the role of disc degeneration. Pain 2007;131:272-80. Sambrook PN, MacGregor AJ, Spector TD. Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 1999;42:366-72. Solovieva S, Lohiniva J, Leino-Arjas P, Raininko R, Luoma K, Ala-Kokko L, et al. COL9A3 gene polymorphism and obesity in intervertebral disc degeneration of the lumbar spine: evidence of gene-environment interaction. Spine (Phila Pa 1976) 2002;27:2691-6. Jiang K, Li Y, Cao GY, Liu D, Liao DF, Gong K, et al. Screening of genes related with intervertebral disc disease by dynamic differential interaction network analysis. Eur Rev Med Pharmacol Sci 2013;17:3186-91. Tabor HK, Risch NJ, Myers RM. Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 2002;3:391-7. Tang Y, Wang S, Liu Y, Wang X. Microarray analysis of genes and gene functions in disc degeneration. Exp Ther Med 2014;7:343-48. Kirkaldy-Willis WH, Wedge JH, Yong-Hing K, Reilly J. Pathology and pathogenesis of lumbar spondylosis and stenosis. Spine (Phila Pa 1976) 1978;3:319-28. Rajasekaran S, Venkatadass K, Naresh Babu J, Ganesh K, Shetty AP. Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs: Results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs. Eur Spine J 2008;17:626-43. Iatridis JC, ap Gwynn I. Mechanisms for mechanical damage in the intervertebral disc annulus fibrosus. J Biomech 2004;37:1165-75. Eyre DR, Muir H. Quantitative analysis of types I and II collagens in human intervertebral discs at various ages. Biochim Biophys Acta 1977;492:29-42. Genetic Home Reference, your guide to undersatanding genetic conditions COL1A1; 2012. Available from: [Last updated on 2013 Apr]. Pluijm SM, van Essen HW, Bravenboer N, Uitterlinden AG, Smit JH, Pols HA, Lips P.Association between an aggrecan gene polymorphism and lumbar disc degeneration. Ann Rheum Dis 2004;63:71-7. Tilkeridis C, Bei T, Garantziotis S, Stratakis CA. Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits. J Med Genet 2005;42:e44. Bei T, Tilkeridis C, Garantziotis S, Boikos SA. A novel, non-functional, COL1A1 polymorphism is not associated with lumbar disk disease in young male Greek subjects unlike that of the Sp1 site. Hormones (Athens) 2008;7:251-4. Schneiderman G, Flannigan B, Kingston S, Thomas J, Dillin WH, Watkins RG. Magnetic resonance imaging in the diagnosis of disc degeneration: Correlation with discography. Spine (Phila Pa 1976) 1987;12:276-81. Kellgren JH. Atlas. Vol. II. Oxford, United Kingdom: Blackwell Scientific Publishers; 1963. Vattam KK, Khan IA, Movva S, Mukkavali KK, Poornima S, Rao P, et al. IGF2 ApaI A/G polymorphism evaluated in ESRD individuals as a biomarker to identify patients with New Onset Diabetes Mellitus after Renal Transplant in Asian Indians. Open J Nephrol 2013;3:104-8. Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 1996;14:203-5. Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, et al. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001;107:899-907. Kiran KV, Mukkavilli KK, Moova S, Upendram P, Saha TK, Rao P, , et al. Influence of gene polymorphism on the pharmacokinetics of calcineurin inhibitors: In renal transplant patients from India. Int Res J Pharm Pharmacol 2013;3:9-15. Khan IA, Movva S, Shaik NA, Chava S, Jahan P, Mukkavali KK, et al. Investigation of Calpain 10 (rs2975760) gene polymorphism in Asian Indians with Gestational Diabetes Mellitus. Meta Gene 2014;2:299-306. Mayer JE, Iatridis JC, Chan D, Qureshi SA, Gottesman O, Hecht AC. Genetic polymorphisms associated with intervertebral disc degeneration. Spine J 2013;13:299-317. Uitterlinden AG, Burger H, Huang Q, Yue F, McGuigan FE, Grant SF, et al. 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 1998;338:1016-21. Sainz J, Van Tornout JM, Sayre J, Kaufman F, Gilsanz V. Association of collagen type 1 alpha1 gene polymorphism with bone density in early childhood. J Clin Endocrinol Metab 1999;84:853-5. Videman T, Saarela J, Kaprio J, Näkki A, Levälahti E, Gill K, et al. Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing. Arthritis Rheum 2009;60:470-81. Rathod TN, Chandanwale AS, Gujrathi S, Patil V, Chavan SA, Shah MN. Association between single nucleotide polymorphism in collagen IX and intervertebral disc disease in the Indian population. Indian J Orthop 2012;46:420-6.

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy