聚集蛋白代谢通路基因多态性与腰椎间盘突出严重程度的相关性
|
摘要
背景:椎间盘突出是一种复杂的脊柱疾病,与椎间盘退变密切相关,而聚集蛋白聚糖的代谢途径的候选基因可能与腰椎间盘突出的严重程度相关。目的:评估单核苷酸变异和慢性机械性腰痛患者腰椎间盘突出严重程度的蛋白聚糖的代谢途径的基因的关联。方法:对60例慢性机械性腰痛患者进行了分类描述研究。T2加权正中矢状位腰椎MRI扫描评估椎间盘突出和椎间盘退变的严重程度。对凝集素代谢途径的2个候选基因(蛋白聚糖和基质金属蛋白酶3)的20个外显子单核苷酸变异进行了基因分型。对年龄、性别、体质量指数和椎间盘退变程度进行多元线性回归分析。试验于2015-03-01经定州市人民医院伦理委员会批准(批准号2015002)。结果与结论:蛋白聚糖的rs2272023、rs938609、rs2882676、rs698621、rs3825994、rs1042630和rs3817428突变体及其单倍型与腰椎间盘突出的严重程度有关。若要确定这些重要的单核苷酸变异在椎间盘突出症的发病机制中的作用,有必要进行功能遗传方面的研究。
BACKGROUND: Protrusion of intervertebral disc is a complex spinal disease, which is closely related to the degeneration of intervertebral disc. Candidate genes of aggregation proteoglycan metabolic pathway may be related to the severity of protrusion of lumbar intervertebral disc.OBJECTIVE: To assess the association between single nucleotide variants and proteoglycan metabolic pathways in the severity of lumbar disc herniation in patients with chronic mechanical low back pain.METHODS: Sixty patients were classified and described. T2-weighted median sagittal lumbar MRI scans were used to assess the severity of disc herniation and degeneration. Single nucleotide variants genotyping of 20 exons of two candidate genes(proteoglycan, matrix metalloproteinase 3) of lectin metabolic pathway was performed. Age, sex, body mass index and the degree of intervertebral disc degeneration were analyzed by multiple linear regression. The trial was approved by the Ethics Committee of People's Hospital of Dingzhou on March 1, 2015(approval No. 2015002).RESULTS AND CONCLUSION: The mutants and haplotypes of rs2272023, rs938609, rs2882676, rs698621, rs3825994, rs1042630 and rs3817428 of proteoglycan are related to the severity of lumbar disc herniation. The single nucleotide variants and its haplotype of proteoglycan are related to the severity of lumbar disc herniation. To determine the role of these important single nucleotide variants in the pathogenesis of intervertebral disc herniation, functional genetic studies are necessary.
BACKGROUND: Protrusion of intervertebral disc is a complex spinal disease, which is closely related to the degeneration of intervertebral disc. Candidate genes of aggregation proteoglycan metabolic pathway may be related to the severity of protrusion of lumbar intervertebral disc.OBJECTIVE: To assess the association between single nucleotide variants and proteoglycan metabolic pathways in the severity of lumbar disc herniation in patients with chronic mechanical low back pain.METHODS: Sixty patients were classified and described. T2-weighted median sagittal lumbar MRI scans were used to assess the severity of disc herniation and degeneration. Single nucleotide variants genotyping of 20 exons of two candidate genes(proteoglycan, matrix metalloproteinase 3) of lectin metabolic pathway was performed. Age, sex, body mass index and the degree of intervertebral disc degeneration were analyzed by multiple linear regression. The trial was approved by the Ethics Committee of People's Hospital of Dingzhou on March 1, 2015(approval No. 2015002).RESULTS AND CONCLUSION: The mutants and haplotypes of rs2272023, rs938609, rs2882676, rs698621, rs3825994, rs1042630 and rs3817428 of proteoglycan are related to the severity of lumbar disc herniation. The single nucleotide variants and its haplotype of proteoglycan are related to the severity of lumbar disc herniation. To determine the role of these important single nucleotide variants in the pathogenesis of intervertebral disc herniation, functional genetic studies are necessary.
引文
[1]马信龙.腰椎间盘突出症的病理学分型及其临床意义[J].实用骨科杂志,2016,22(4):384.
[2]Perera RS,Dissanayake PH,Senarath U,et al.Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes.PLoSOne.2017;12(1):e0169835.
[3]高克海,李洪涛,黄彩虹.聚集蛋白聚糖酶-1在退变椎间盘中的表达及意义[J].中国矫形外科杂志,2014,22(15):1412-1416.
[4]耿翔,吕国华.聚集蛋白聚糖基因多态性与腰椎间盘退变相关性的研究进展[J].中国脊柱脊髓杂志,2013,23(4):370-372.
[5]Cong L,Zhu Y,Pang H,et al.The interaction between aggrecan gene VNTR polymorphism and obesity in predicting incident symptomatic lumbar disc herniation.Connect Tissue Res.2014;55(5-6):384-390.
[6]李峰,廖泉森,杨新海.MMP3与腰椎间盘突出症间盘突出程度的相关性研究[J].新疆医学,2010,40(2):43-46.
[7]丛琳,朱悦,屠冠军.聚集蛋白聚糖基因串联重复多态性与腰椎间盘突出症相关性研究[J].中华外科杂志,2015,53(2):116-120.
[8]蒋家耀,卢旭华.椎间盘退变生物学治疗的研究进展[J].中国骨伤,2016,29(6):576-580.
[9]王毅翔,吴爱悯,Santiago FR.腰痛患者如何选择影像学检查的循证医学依据[J].重庆医学,2018,47(18):2389-2398.
[10]Omair A,Holden M,Lie BA,et al.Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants:a prospective genetic association study.BMC Musculoskelet Disord.2013;14:105.
[11]李国强.基于医学指标与体质量指数关系评价肥胖标准的方法[J].中国组织工程研究,2007,11(43):8745-8748.
[12]Lane NE,Nevitt MC,Genant HK,et al.Reliability of new indices of radiographic osteoarthritis of the hand and hip and lumbar disc degeneration.J Rheumatol.1993;20(11):1911-1918.
[13]王蓉,杜永浩,杨健,等.腰椎间盘退变MRI分级系统的一致性评价[J].实用放射学杂志,2016,32(11):1740-1744.
[14]杨占辉,孙建华,丁浩.腰椎间盘突出症的评分法疗效评定标准[J].颈腰痛杂志,1999(1):20-21.
[15]孙博.非同义突变对蛋白质翻译后修饰的影响及其在人类疾病中的意义[D].上海:上海交通大学,2015.
[16]Katsonis P,Koire A,Wilson SJ,et al.Single nucleotide variations:biological impact and theoretical interpretation.Protein Sci.2014;23(12):1650-1666.
[17]耿翔.人聚蛋白聚糖基因多态性与腰椎间盘退变性疾病的相关性[D].长沙:中南大学,2013.
[18]薛静波,王文军,晏怡果,等.骨保护素基因多态性与椎间盘退变的相关性研究[J].中国骨科临床与基础研究杂志,2016,8(6):352-358.
[19]Huang X,Chen F,Zhao J,et al.Interleukin 6(IL-6)and IL-10 Promoter Region Polymorphisms Are Associated with Risk of Lumbar Disc Herniation in a Northern Chinese Han Population.Genet Test Mol Biomarkers.2017;21(1):17-23.
[20]Eser B,Eser O,Yuksel Y,et al.Effects of MMP-1 and MMP-3 gene polymorphisms on gene expression and protein level in lumbar disc herniation.Genet Mol Res.2016;15(3).
[21]路康,杨匡,李海音,等.髓核细胞来源外泌体对骨髓间充质干细胞向髓核样细胞分化的作用[J].中国脊柱脊髓杂志,2016,26(10):933-938.
[22]Videman T,Saarela J,Kaprio J,et al.Associations of 25 structural,degradative,and inflammatory candidate genes with lumbar disc desiccation,bulging,and height narrowing.Arthritis Rheum.2009;60(2):470-481.
[23]Smith LJ,Nerurkar NL,Choi KS,et al.Degeneration and regeneration of the intervertebral disc:lessons from development.Dis Model Mech.2011;4(1):31-41.
[24]Kepler CK,Anderson DG,Tannoury C,et al.Intervertebral disk degeneration and emerging biologic treatments.J Am Acad Orthop Surg.2011;19(9):543-553.
[25]谭平先,李健,孙筱放,等.聚集蛋白聚糖基因多态性与腰椎间盘突出症的关联性[J].中国组织工程研究,2011,15(33):6257-6261.
[26]肖飞,刘国辉.椎间盘退变的遗传学机制研究进展[J].中国矫形外科杂志,2007,15(21):1632-1634.
[2]Perera RS,Dissanayake PH,Senarath U,et al.Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes.PLoSOne.2017;12(1):e0169835.
[3]高克海,李洪涛,黄彩虹.聚集蛋白聚糖酶-1在退变椎间盘中的表达及意义[J].中国矫形外科杂志,2014,22(15):1412-1416.
[4]耿翔,吕国华.聚集蛋白聚糖基因多态性与腰椎间盘退变相关性的研究进展[J].中国脊柱脊髓杂志,2013,23(4):370-372.
[5]Cong L,Zhu Y,Pang H,et al.The interaction between aggrecan gene VNTR polymorphism and obesity in predicting incident symptomatic lumbar disc herniation.Connect Tissue Res.2014;55(5-6):384-390.
[6]李峰,廖泉森,杨新海.MMP3与腰椎间盘突出症间盘突出程度的相关性研究[J].新疆医学,2010,40(2):43-46.
[7]丛琳,朱悦,屠冠军.聚集蛋白聚糖基因串联重复多态性与腰椎间盘突出症相关性研究[J].中华外科杂志,2015,53(2):116-120.
[8]蒋家耀,卢旭华.椎间盘退变生物学治疗的研究进展[J].中国骨伤,2016,29(6):576-580.
[9]王毅翔,吴爱悯,Santiago FR.腰痛患者如何选择影像学检查的循证医学依据[J].重庆医学,2018,47(18):2389-2398.
[10]Omair A,Holden M,Lie BA,et al.Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants:a prospective genetic association study.BMC Musculoskelet Disord.2013;14:105.
[11]李国强.基于医学指标与体质量指数关系评价肥胖标准的方法[J].中国组织工程研究,2007,11(43):8745-8748.
[12]Lane NE,Nevitt MC,Genant HK,et al.Reliability of new indices of radiographic osteoarthritis of the hand and hip and lumbar disc degeneration.J Rheumatol.1993;20(11):1911-1918.
[13]王蓉,杜永浩,杨健,等.腰椎间盘退变MRI分级系统的一致性评价[J].实用放射学杂志,2016,32(11):1740-1744.
[14]杨占辉,孙建华,丁浩.腰椎间盘突出症的评分法疗效评定标准[J].颈腰痛杂志,1999(1):20-21.
[15]孙博.非同义突变对蛋白质翻译后修饰的影响及其在人类疾病中的意义[D].上海:上海交通大学,2015.
[16]Katsonis P,Koire A,Wilson SJ,et al.Single nucleotide variations:biological impact and theoretical interpretation.Protein Sci.2014;23(12):1650-1666.
[17]耿翔.人聚蛋白聚糖基因多态性与腰椎间盘退变性疾病的相关性[D].长沙:中南大学,2013.
[18]薛静波,王文军,晏怡果,等.骨保护素基因多态性与椎间盘退变的相关性研究[J].中国骨科临床与基础研究杂志,2016,8(6):352-358.
[19]Huang X,Chen F,Zhao J,et al.Interleukin 6(IL-6)and IL-10 Promoter Region Polymorphisms Are Associated with Risk of Lumbar Disc Herniation in a Northern Chinese Han Population.Genet Test Mol Biomarkers.2017;21(1):17-23.
[20]Eser B,Eser O,Yuksel Y,et al.Effects of MMP-1 and MMP-3 gene polymorphisms on gene expression and protein level in lumbar disc herniation.Genet Mol Res.2016;15(3).
[21]路康,杨匡,李海音,等.髓核细胞来源外泌体对骨髓间充质干细胞向髓核样细胞分化的作用[J].中国脊柱脊髓杂志,2016,26(10):933-938.
[22]Videman T,Saarela J,Kaprio J,et al.Associations of 25 structural,degradative,and inflammatory candidate genes with lumbar disc desiccation,bulging,and height narrowing.Arthritis Rheum.2009;60(2):470-481.
[23]Smith LJ,Nerurkar NL,Choi KS,et al.Degeneration and regeneration of the intervertebral disc:lessons from development.Dis Model Mech.2011;4(1):31-41.
[24]Kepler CK,Anderson DG,Tannoury C,et al.Intervertebral disk degeneration and emerging biologic treatments.J Am Acad Orthop Surg.2011;19(9):543-553.
[25]谭平先,李健,孙筱放,等.聚集蛋白聚糖基因多态性与腰椎间盘突出症的关联性[J].中国组织工程研究,2011,15(33):6257-6261.
[26]肖飞,刘国辉.椎间盘退变的遗传学机制研究进展[J].中国矫形外科杂志,2007,15(21):1632-1634.