Genetic Alterations in Intervertebral Disc Disease.
Genetic Alterations in Intervertebral Disc Disease.
复制标题
DOI：
10.3389/fsurg.2016.00059
复制
发表时间：
2016
影响因子：
1.8
通讯作者：
Theodore N
中科院分区：
文献类型：
--
作者：
Martirosyan NL;Patel AA;Carotenuto A;Kalani MY;Belykh E;Walker CT;Preul MC;Theodore N
椎间盘退变（IVDD）被认为是一种受环境和遗传因素影响的多因素疾病。近二十年的研究表明，遗传因素约占IVDD病因的75%。最近的全基因组测序研究揭示了与IVDD相关的各种单核苷酸多态性（SNP）。本文综述了有关IVDD中涉及的炎症、降解、稳态和结构系统中遗传因素多样性的全面和最新信息。提供了关于已确定影响IVDD发生风险的遗传多态性的有组织的信息收集。了解参与IVDD的蛋白质和信号系统可以提高对治疗方法的理解和靶向。使用国家医学图书馆进行电子文献检索，检索关键词为IVDD遗传学、腰椎间盘退变、退行性椎间盘疾病、多态性、SNP和椎间盘疾病。然后根据纳入标准筛选文章，包括涵盖SNP与发展IVDD相关性的主题。65篇文章被确定为包含相关信息。如果研究腰痛或仅研究椎间盘突出而未分析椎间盘退变，则排除文献。本研究的重点是IVD的慢性变性。各种基因被鉴定为含有影响发展IVDD风险的SNP。这些基因中包括结构蛋白基因，如COL 1A 1、COL 9A 3、COL 9A 3、COL 11 A1和COL 11 A2、ACAN和CHST 3。此外，在维生素D受体基因中发现的各种SNP也与IVDD相关。与炎性细胞因子失衡相关的SNP与IVDD相关，尽管一些影响受到性别和某些人群的限制。编码细胞外基质降解酶（如MMP-1、MMP-2、MMP-3、MMP-9、MMP-14、ADAMTS-4和ADAMTS-5）的基因中的SNP也与IVDD相关。凋亡介导基因，如caspase 9基因（CASP 9），TRAIL和死亡受体4（DR 4），以及生长因子，如生长分化因子5和VEGF，被鉴定为具有影响发展IVDD风险的多态性。在过去的10年里，在以前未知的与IVDD相关的基因中发现了无数新的SNP。此外，在过去的十年中，还发现了已知与IVDD风险增加有关的基因中的新SNP。进一步了解IVDD的各种病理生理学因素背后的许多遗传变异，有助于推动未来IVDD患者的个性化护理和药物治疗策略。
Intervertebral disc degeneration (IVDD) is considered a multifactorial disease that is influenced by both environmental and genetic factors. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single-nucleotide polymorphisms (SNPs) that are associated with IVDD. This review presents comprehensive and updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD. An organized collection of information is provided regarding genetic polymorphisms that have been identified to influence the risk of developing IVDD. Understanding the proteins and signaling systems involved in IVDD can lead to improved understanding and targeting of therapeutics. An electronic literature search was performed using the National Library of Medicine for publications using the keywords genetics of IVDD, lumbar disc degeneration, degenerative disc disease, polymorphisms, SNPs, and disc disease. The articles were then screened based on inclusion criteria that included topics that covered the correlation of SNPs with developing IVDD. Sixty-five articles were identified as containing relevant information. Articles were excluded if they investigated lower back pain or just disc herniation without an analysis of disc degeneration. This study focuses on the chronic degeneration of IVDs. Various genes were identified to contain SNPs that influenced the risk of developing IVDD. Among these are genes contributing to structural proteins, such as COL1A1, COL9A3, COL9A3, COL11A1, and COL11A2, ACAN, and CHST3. Furthermore, various SNPs found in the vitamin-D receptor gene are also associated with IVDD. SNPs related to inflammatory cytokine imbalance are associated with IVDD, although some effects are limited by sex and certain populations. SNPs in genes that code for extracellular matrix-degrading enzymes, such as MMP-1, MMP-2, MMP-3, MMP-9, MMP-14, ADAMTS-4, and ADAMTS-5 are also associated with IVDD. Apoptosis-mediating genes, such as caspase 9 gene (CASP9), TRAIL, and death receptor 4 (DR4), as well as those for growth factors, such as growth differentiation factor 5 and VEGF, are identified to have polymorphisms that influence the risk of developing IVDD. Within the last 10 years, countless new SNPs have been identified in genes previously unknown to be associated with IVDD. Furthermore, the last decade has also revealed new SNPs identified in genes already known to be involved with increased risk of developing IVDD. Improved understanding of the numerous genetic variants behind various pathophysiological elements of IVDD could help advance personalized care and pharmacotherapeutic strategies for patients suffering from IVDD in the future.
登录
查看更多内容
影响因子：
2.8
作者：
Dong, D. M.;Yao, M.;Wang, Y. S.
通讯作者：
Wang, Y. S.
Caspase-9启动子区多态性与椎间盘源性腰痛的关联
影响因子：
2.9
作者：
Guo, Tuan-Mao;Liu, Miao;Wu, Shi-Xun
通讯作者：
Wu, Shi-Xun
影响因子：
2.8
作者：
Mu, Jihong;Ge, Weiming;Huang, Changlin
通讯作者：
Huang, Changlin
DOI：
10.1016/j.spinee.2013.01.041
发表时间：
2013-03
期刊：
The spine journal : official journal of the North American Spine Society
影响因子：
--
作者：
Mayer JE;Iatridis JC;Chan D;Qureshi SA;Gottesman O;Hecht AC
通讯作者：
Hecht AC
影响因子：
7.4
作者：
Noponen-Hietala, N;Virtanen, L;Ala-Kokko, L
通讯作者：
Ala-Kokko, L