Interleukin 1 polymorphisms and intervertebral disc degeneration.

Department of Epidemiology and Biostatistics, Finnish Institute of Occupational Health, Helsinki, Finland.
Epidemiology (Impact Factor: 6.2). 10/2004; 15(5):626-33.
Source: PubMed


Enzymatic breakdown of the extracellular matrix, and possibly local inflammation, contributes to intervertebral disc degeneration. We investigated whether polymorphisms within the IL-1 gene locus are associated with lumbar disc degeneration and whether the effect of occupational physical load on disc degeneration is modified by the polymorphisms.
Genotypes were determined from 133 middle-aged men who underwent magnetic resonance imaging of the lumbar spine. The participants represented 3 occupations: 40 were machine drivers, 42 carpenters, and 51 office workers. We evaluated decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration in the L2/L3-L5/S1 discs.
The odds ratio for disc bulges was 2.4 (95% confidence interval = 1.2-4.8) and 1.9 (1.0-3.7), in carriers of the IL-1alphaT or IL-1betaT alleles, respectively. The TT genotype of the IL-1alpha gene carried more than 3-fold risk of disc bulges as compared with the CC genotype.
IL-1 gene cluster polymorphisms could affect the risk of disc degeneration. The effect of physical workload seems to be modified by the IL-1 gene polymorphisms.

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    • "IL-1í µí»¼ is a proinflammatory cytokine involved in the regulation of immune responses, inflammatory processes, hematopoiesis, and induction of apoptosis in response to cell injury. IL-1í µí»¼, produced mainly by activated macrophages, neutrophils, and epithelial and endothelial cells, is thought to be involved in the pathogenesis of disc degeneration by increasing the production of ECM degradation enzymes and by inhibiting ECM synthesis [36] [37] [38]. Some polymorphisms of the IL-1í µí»¼ gene (IL1A) have been associated with disc degeneration [30] [39]. "
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    ABSTRACT: Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.
    International Journal of Plant Genomics 11/2014; 2014:7. DOI:10.1155/2014/302568
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    • "IL1α, IL1β and IL1Ra and their composite genotype have previously been linked to disc degeneration and low back pain in the general population [8], [9]. We hypothesized that patients with a high expression of IL1α (carriers of rs1800587 T allele) or high expression of IL1β (carriers of rs1143627 T allele), combined with a reduced expression of IL1Ra (carriers of rs2234677 A allele), would have an increased risk of long-lasting clinical pain as well. "
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    ABSTRACT: Previous studies indicate that lumbar radicular pain following disc herniation may be associated with release of several pro-inflammatory mediators, including interleukin-1 (IL1). In the present study, we examined how genetic variability in IL1A (rs1800587 C>T), IL1B (rs1143627 T>C) and IL1RN (rs2234677 G>A) influenced the clinical outcome the first year after disc herniation. Patients (n = 258) with lumbar radicular pain due to disc herniation were recruited from two hospitals in Norway. Pain and disability were measured by visual analogue scale (VAS) and Oswestry Disability Index (ODI) over a 12 month period. The result showed that patients with the IL1A T allele, in combination with the IL1RN A allele had more pain and a slower recovery than other patients (VAS p = 0.049, ODI p = 0.059 rmANOVA; VAS p = 0.003, ODI p = 0.050 one-way ANOVA at 12 months). However, regarding the IL1B/IL1RN genotype, no clear effect on recovery was observed (VAS p = 0.175, ODI p = 0.055 rmANOVA; VAS p = 0.105, ODI p = 0.214 one-way ANOVA at 12 months). The data suggest that the IL1A T/IL1RN A genotype, but not the IL1B T/IL1RN A genotype, may increase the risk of a chronic outcome in patients following disc herniation.
    PLoS ONE 09/2014; 9(9):e107301. DOI:10.1371/journal.pone.0107301 · 3.23 Impact Factor
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    • "Polymorphisms of the vitamin D receptor gene (Videman et al., 1998), collagen IX alleles (Annunen et al., 1999) and metalloprotease-3 (MMP-3) (Takahashi et al., 2001) and variations in the chondroitin sulphate-1 domain of the aggrecan gene (Kawaguchi et al., 1999) are demonstrated to be related to IDD. Moreover, single nucleotide polymorphisms that inhibit growth factors, such as transforming growth factor-b (TGFb) (Seki et al., 2005), and alleles that code for interleukin-1 (IL-1) (Solovieva et al., 2004) have been also described. The imbalance between synthesis and catabolism of crucial ECM components contributes to IDD (Smith et al., 2011). "
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    ABSTRACT: Low back pain is one of the major health problems in industrialized countries, as a leading source of disability in the working population. Intervertebral disc degeneration has been identified as its main cause, being a progressive process mainly characterized by alteration of extracellular matrix composition and water content. Many factors are involved in the degenerative cascade, such as anabolism/catabolism imbalance, reduction of nutrition supply and progressive cell loss. Currently available treatments are symptomatic, and surgical procedures consisting of disc removal are often necessary. Recent advances in our understanding of intervertebral disc biology led to an increased interest in the development of novel biological treatments aimed at disc regeneration. Growth factors, gene therapy, stem cell transplantation and biomaterials-based tissue engineering might support intervertebral disc regeneration by overcoming the limitation of the self-renewal mechanism. The aim of this paper is to overview the literature discussing the current status of our knowledge from the degenerative cascade of the intervertebral disc to the latest molecular, cell-based therapies and tissue-engineering strategies for disc regeneration. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 03/2013; 9(6). DOI:10.1002/term.1719 · 5.20 Impact Factor
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