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      Gene polymorphisms and expression levels of interleukin-6 and interleukin-10 in lumbar disc disease: a meta-analysis and immunohistochemical study

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          Abstract

          Background

          To investigate the association between interleukin-6 (IL-6) (rs1800795, rs1800796, rs1800797, rs13306435, rs2069849) and interleukin-10 (IL-10) (rs1800871, rs1800896) gene polymorphisms, expression levels, and lumbar disc disease (LDD).

          Methods

          We conducted a literature research on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) until February 28, 2019. We included all case-control studies about the association between IL-6 and IL-10 gene polymorphisms and LDD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of association. Statistical analysis was conducted by Review Manager (RevMan) 5.3 software. Furthermore, immunohistochemistry (IHC) and RT-PCR were performed to evaluate IL-6 and IL-10 expressions in the normal and degenerated disc.

          Results

          A total of 6 studies, involving 1456 cases and 1611 controls, were included in this meta-analysis. G alleles of rs1800795 and rs1800797 in the IL-6 gene were significantly associated with LDD (rs1800795: G vs. C, OR = 1.38, 95% CI = 1.16–1.64, P = 0.0002; rs1800797: G vs. A, OR = 1.35, 95% CI = 1.14–1.61, P = 0.0006). Begg’s funnel plot and Egger’s tests did not show any evidence of publication bias. IL-6 expression and IL-6 mRNA levels were significantly increased in the degenerated disc compared with those in the normal disc (IL-6 immunopositive cells, 73.68 ± 10.99% vs. 37.23 ± 6.42%, P < 0.001).

          Conclusions

          IL-6 gene polymorphisms (rs1800795 and rs1800797) were significantly associated with susceptibility to LDD. A high expression level of IL-6 may be an important risk factor for LDD.

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          Most cited references33

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          Role of cytokines in intervertebral disc degeneration: pain and disc content.

          Degeneration of the intervertebral discs (IVDs) is a major contributor to back, neck and radicular pain. IVD degeneration is characterized by increases in levels of the proinflammatory cytokines TNF, IL-1α, IL-1β, IL-6 and IL-17 secreted by the IVD cells; these cytokines promote extracellular matrix degradation, chemokine production and changes in IVD cell phenotype. The resulting imbalance in catabolic and anabolic responses leads to the degeneration of IVD tissues, as well as disc herniation and radicular pain. The release of chemokines from degenerating discs promotes the infiltration and activation of immune cells, further amplifying the inflammatory cascade. Leukocyte migration into the IVD is accompanied by the appearance of microvasculature tissue and nerve fibres. Furthermore, neurogenic factors, generated by both disc and immune cells, induce expression of pain-associated cation channels in the dorsal root ganglion. Depolarization of these ion channels is likely to promote discogenic and radicular pain, and reinforce the cytokine-mediated degenerative cascade. Taken together, an enhanced understanding of the contribution of cytokines and immune cells to these catabolic, angiogenic and nociceptive processes could provide new targets for the treatment of symptomatic disc disease. In this Review, the role of key inflammatory cytokines during each of the individual phases of degenerative disc disease, as well as the outcomes of major clinical studies aimed at blocking cytokine function, are discussed.
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            Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study.

            The purposes of this study were to investigate the prevalence and distribution of intervertebral disc degeneration (DD) over the entire spine using magnetic resonance imaging (MRI), and to examine the factors and symptoms potentially associated with DD.
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              Cytokine and cytokine receptor gene polymorphisms and their functionality.

              Cytokines, signaling proteins produced by a variety of cell types, are essential for the development and functioning of both innate and adaptive immune response. Cytokine gene expression is tightly regulated, and aberrant expression from environmental and genetic polymorphism has been implicated in a range of diseases, susceptibility to infections, and responses to treatment. This review concentrates on the functionality of cytokine and cytokine receptor gene polymorphisms; it is through these variants that genuine disease-associations are based. Several mechanisms for single nucleotide polymorphism (SNP) functionality are present within cytokine genes including: amino acid changes (IL-6R, IL-13, IL-1alpha), exon skipping (IL-7Ralpha), proximal promoter variants (IL-1beta, IL-Ra, IL-2, IL-6, IL-10, IL-12, IL-13, IL-16, TNF, IFN-gamma, TGF-beta), distal promoter variants (IL-6, IL-18) and intronic enhancer variants (IL-8).
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                Author and article information

                Contributors
                754258289@qq.com
                9750125@qq.com
                569610781@qq.com
                827066327@qq.com
                1106408235@qq.com
                gxspine@163.com
                drjianghua@163.com
                Journal
                J Orthop Surg Res
                J Orthop Surg Res
                Journal of Orthopaedic Surgery and Research
                BioMed Central (London )
                1749-799X
                18 February 2020
                18 February 2020
                2020
                : 15
                : 54
                Affiliations
                [1 ]GRID grid.412594.f, Division of Spine Surgery, , The First Affiliated Hospital of Guangxi Medical University, ; No.6 Shuangyong Road, Nanning, 530021 China
                [2 ]GRID grid.412594.f, Department of Orthopaedic Surgery, , The First Affiliated Hospital of Guangxi Medical University, ; No.6 Shuangyong Road, Nanning, 530021 China
                Author information
                http://orcid.org/0000-0001-9347-5782
                Article
                1588
                10.1186/s13018-020-01588-8
                7027108
                32070384
                dc89f835-a302-4fc7-abe8-5e8311e0e215
                © The Author(s) 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 September 2019
                : 11 February 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81860406
                Award ID: 81460353
                Award ID: 81560371
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004607, Natural Science Foundation of Guangxi Province;
                Award ID: 2018GXNSFAA281127
                Award ID: 2015GXNSFBA139167
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Surgery
                il-6,il-10,lumbar disc disease,meta-analysis,polymorphisms
                Surgery
                il-6, il-10, lumbar disc disease, meta-analysis, polymorphisms

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