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      Fat Mass and Obesity-Associated ( FTO) Gene Polymorphisms Are Associated with Risk of Intervertebral Disc Degeneration in Chinese Han Population: A Case Control Study

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          Abstract

          Background

          The present study aimed to evaluate whether the fat mass and obesity-associated ( FTO) gene polymorphisms are associated with risk of intervertebral disc degeneration (IDD) in a largest Chinese Han population.

          Material/Methods

          There were 502 IDD patients and 497 healthy controls enrolled in this study. Nineteen single nucleotide polymorphisms (SNPs) in the FTO gene were tested using the Sequenom MassARRAY platform. The Hardy-Weinberg equilibrium test, followed by allelic, genotypic, haplotypic association, and SNP interaction analyses were used for SNP evaluation. The Genotype-Tissue Expression (GTEx) database was used to evaluate expression quantitative trait loci (eQTL) value of polymorphism. Spearman rank correlation and logistic regression analyses were used for assessing the internal relation between genotypic changes and the risk of IDD.

          Results

          Seventeen SNPs survived the Hardy-Weinberg equilibrium test. Allelic analysis showed that allele T of SNP rs1121980 was a risk allele. Haplotypic and SNP interaction analyses suggested that 2 haplotypes and 5 SNP combinations were associated with the predisposition of IDD respectively. GTEx database revealed that the SNP rs1121980 might interfere with the expression of the FTO gene in the muscle-skeletal system. Through clinical statistics analysis, the different genotypes of rs1121980 can present different disease severity of IDD.

          Conclusions

          Our study suggests that rs1121980 can become a biomarker for the screening and prognosis of IDD. The 2 haplotype blocks and 5 SNP-SNP combinations that we discovered might be indicative of the onset of IDD. Therefore, our study might serve as evidence for future IDD molecular diagnosis.

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          Most cited references34

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          What is intervertebral disc degeneration, and what causes it?

          Review and reinterpretation of existing literature. To suggest how intervertebral disc degeneration might be distinguished from the physiologic processes of growth, aging, healing, and adaptive remodeling. The research literature concerning disc degeneration is particularly diverse, and there are no accepted definitions to guide biomedical research, or medicolegal practice. The process of disc degeneration is an aberrant, cell-mediated response to progressive structural failure. A degenerate disc is one with structural failure combined with accelerated or advanced signs of aging. Early degenerative changes should refer to accelerated age-related changes in a structurally intact disc. Degenerative disc disease should be applied to a degenerate disc that is also painful. Structural defects such as endplate fracture, radial fissures, and herniation are easily detected, unambiguous markers of impaired disc function. They are not inevitable with age and are more closely related to pain than any other feature of aging discs. Structural failure is irreversible because adult discs have limited healing potential. It also progresses by physical and biologic mechanisms, and, therefore, is a suitable marker for a degenerative process. Biologic progression occurs because structural failure uncouples the local mechanical environment of disc cells from the overall loading of the disc, so that disc cell responses can be inappropriate or "aberrant." Animal models confirm that cell-mediated changes always follow structural failure caused by trauma. This definition of disc degeneration simplifies the issue of causality: excessive mechanical loading disrupts a disc's structure and precipitates a cascade of cell-mediated responses, leading to further disruption. Underlying causes of disc degeneration include genetic inheritance, age, inadequate metabolite transport, and loading history, all of which can weaken discs to such an extent that structural failure occurs during the activities of daily living. The other closely related definitions help to distinguish between degenerate and injured discs, and between discs that are and are not painful.
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            Inactivation of the Fto gene protects from obesity.

            Several independent, genome-wide association studies have identified a strong correlation between body mass index and polymorphisms in the human FTO gene. Common variants in the first intron define a risk allele predisposing to obesity, with homozygotes for the risk allele weighing approximately 3 kilograms more than homozygotes for the low risk allele. Nevertheless, the functional role of FTO in energy homeostasis remains elusive. Here we show that the loss of Fto in mice leads to postnatal growth retardation and a significant reduction in adipose tissue and lean body mass. The leanness of Fto-deficient mice develops as a consequence of increased energy expenditure and systemic sympathetic activation, despite decreased spontaneous locomotor activity and relative hyperphagia. Taken together, these experiments provide, to our knowledge, the first direct demonstration that Fto is functionally involved in energy homeostasis by the control of energy expenditure.
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              Low back pain in relation to lumbar disc degeneration.

              Cross-sectional magnetic resonance imaging (MRI) study. To study the relation of low back pain (LBP) to disc degeneration in the lumbar spine. Controversy still prevails about the relationship between disc degeneration and LBP. Classification of disc degeneration and symptoms varies, hampering comparison of study results. Subjects comprised 164 men aged 40-45 years-53 machine drivers, 51 construction carpenters, and 60 office workers. The data of different types of LBP, individual characteristics, and lifestyle factors were obtained from a questionnaire and a structured interview. Degeneration of discs L2/L3-L5/S1 (dark nucleus pulposus and posterior and anterior bulge) was assessed with MRI. An increased risk of LBP (including all types) was found in relation to all signs of disc degeneration. An increased risk of sciatic pain was found in relation to posterior bulges, but local LBP was not related to disc degeneration. The risks of LBP and sciatic pain were strongly affected by occupation. Low back pain is associated with signs of disc degeneration and sciatic pain with posterior disc bulges. Low back pain is strongly associated with occupation.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2018
                12 August 2018
                : 24
                : 5598-5609
                Affiliations
                [1 ]Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China
                [2 ]Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, P.R. China
                [3 ]Medical Research Center of Orthopedics, Chinese Academy of Medical Sciences, Beijing, P.R. China
                [4 ]Department of Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China
                Author notes
                Corresponding Authors: Nan Wu, e-mail: dr.wunan@ 123456pumch.cn , Guixing Qiu, e-mail: qiuguixingpumch@ 123456126.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                911101
                10.12659/MSM.911101
                6103244
                30099472
                52aae329-b98a-4a47-9806-8995ea8db0b6
                © Med Sci Monit, 2018

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 12 May 2018
                : 16 July 2018
                Categories
                Clinical Research

                genetic linkage,intervertebral disc degeneration,low back pain,polymorphism, single nucleotide,prognosis

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