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      Association between IL4, IL6 gene polymorphism and lumbar disc degeneration in Chinese population

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          Abstract

          Lumbar disc disease (LDD) is a common musculoskeletal disorder, caused by degeneration of intervertebral discs of the lumbar spine and is one of the most common musculoskeletal disorders affliction in adult. There is growing evidence that LDD has strong genetic determinants. We analyze whether the IL4 and IL6 gene polymorphism is related to LDD in Chinese Han population. The participants were 498 with LDD and 463 without LDD. IL4 and IL6 gene polymorphism were determined by Sequenom MassARRAY. We found that SNPs rs1800796(OR = 1.29, 95% CI, 1.07 – 1.57, p = 0.009), rs1524107(OR = 1.28, 95% CI, 1.05 – 1.55, p = 0.013), rs2069840 (OR = 1.39, 95% CI, 1.03 – 1.89, p = 0.033) in IL6 gene were significantly associated with LDD risk at a 5% level. In addition, genetic models found IL4 gene (rs2243250) were associated with LDD. In this study, we analyzed and associated SNPs of IL4 and IL6 with LDD risk. In summary, four variations (rs1800796, rs1524107, rs2069840, rs2243250) of the selected candidate SNPs were associated with susceptibility to LDD in our study. The results of this study have the guiding significance in clinical work in the future in the treatment of lumbar disc herniation patients, not one-sided that the symptoms of low back pain only from mechanical oppression.

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          Most cited references26

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          High-throughput oncogene mutation profiling in human cancer.

          Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.
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            Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators.

            Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p < 0.006 and p < 0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.
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              Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2.

              Herniated lumbar disc specimens were obtained from patients undergoing surgical discectomy for persistent radiculopathy and cultured in vitro to determine whether various biochemical agents were being produced. Our hypothesis is that biochemical mediators of inflammation and tissue degradation play a role in intervertebral disc degeneration and in the pathophysiology of radiculopathy. Low back pain with or without radiculopathy is a significant clinical problem, but the etiology of low back pain and the exact pathophysiology of radiculopathy remain elusive. The biochemical events that occur with intervertebral disc degeneration and, in particular, the role of biochemical mediators of inflammation and tissue degradation have received sparse attention in the literature. There is some preliminary evidence that inflammatory mediators may have an important role in the pathophysiology of radiculopathy. Eighteen herniated lumbar discs were obtained from 15 patients undergoing disc surgery. The specimens were cultured and incubated for 72 hours, and the media were collected subsequently for biochemical analysis. Biochemical assays for matrix metalloproteinases, nitric oxide, prostaglandin E2, and a variety of cytokines were performed. As a control group, eight lumbar disc specimens were obtained from four patients undergoing anterior surgery for scoliosis and traumatic burst fractures, and similar biochemical analyses were performed. The culture media from the herniated lumbar discs showed increased levels of matrix metalloproteinase activity compared with the control discs. Similarly, the levels of nitric oxide, prostaglandin E2, and interleukin-6 were significantly higher in the herniated discs compared with the control discs. Interleukin 1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, interleukin-1 receptor antagonist protein, and substance P were not detected in the culture media of either the herniated or control discs. Herniated lumbar discs were making spontaneously increased amounts of matrix metalloproteinases, nitric oxide, prostaglandin E2, and interleukin-6. These products may be involved intimately in the biochemistry of disc degeneration and the pathophysiology of radiculopathy. Their exact roles certainly need further investigation, but their mere presence implicates biochemical processes in intervertebral disc degeneration.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                24 October 2017
                6 October 2017
                : 8
                : 51
                : 89064-89071
                Affiliations
                1 The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, China
                2 The Hohhot First Hospital, Hohhot 010020, China
                3 Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an 710069, China
                4 The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010020, China
                Author notes
                Correspondence to: Xuejun Yang, yangxjhohhot@ 123456163.com
                [*]

                These authors have contributed equally to this work

                Article
                21650
                10.18632/oncotarget.21650
                5687669
                29179499
                6c208831-0073-467d-8337-08e13529b1ca
                Copyright: © 2017 Zhu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 July 2017
                : 27 August 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                lumbar disc disease (ldd),il4,il6,han chinese,case-control
                Oncology & Radiotherapy
                lumbar disc disease (ldd), il4, il6, han chinese, case-control

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