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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

台湾地区金属蛋白酶-1和-2组织抑制剂多态性与阿尔茨海默病的相关性

卷 18, 期 6, 2021

发表于: 23 September, 2021

页: [505 - 512] 页: 8

弟呕挨: 10.2174/1567205018666210924095818

价格: $65

摘要

背景：阿尔茨海默病 (AD) 导致老龄化人口的进行性神经元丢失以及认知和行为下降。基质金属蛋白酶 (MMPs) 和相关的金属蛋白酶组织抑制剂 (TIMPs) 参与细胞外基质的重塑。 β-42 淀粉样蛋白会破坏神经血管单元的完整性并诱发影响神经元的毒性反应。 目的：本研究调查了 MMP-2、MMP-9、TIMP-1 和 TIMP-2 基因的遗传变异与 AD 之间的关系。 方法：招募了台湾人口的 213 名可能的 AD 患者和 315 名对照参与者进行初步调查，我们使用台湾生物银行 (TWB) 的 763 名参与者的数据作为对照进行验证。对年龄、性别、高血压、糖尿病 (DM) 和饮酒进行了多变量逻辑回归分析。使用 R 的 SNPassoc 包分析了基因型和等位基因频率与 SNP 相关 AD 遗传模型之间的关联。我们使用 1,000 次重复进行了排列测试以进行经验估计。 结果：共招募了 213 名可能的 AD 患者和 315 名对照参与者。 AD 患者中 TIMP-2 中 rs7503726 (G > A) 中 A 等位基因的频率较低 (p < 0.01)。 AD 患者中 TIMP-2 rs7503726 G/A 和 A/A 基因型的频率也显着低于对照组和 TWB（p = 0.02）。 TIMP-2 rs7503726 AA 基因型与 AD 在加性和隐性遗传模型中的保护作用相关（OR = 0.54, 95% CI: 0.32 - 0.92, p = 0.02; OR = 0.68, 95% CI: 0.50, - 0.9 p = 0.01，分别）。 结论：TIMP-2 rs7503726 AA基因型与AD易感性呈负相关，rs7503726的次要等位基因（A等位基因）的存在对AD具有保护作用。

关键词: 阿尔茨海默病、β-淀粉样蛋白、基质金属蛋白酶、单核苷酸多态性、tau、金属蛋白酶组织抑制剂。

« Previous Next »
[1]
2016 Alzheimer’s disease facts and figures. Alzheimers Dement 2016; 12(4): 459-509.
[http://dx.doi.org/10.1016/j.jalz.2016.03.001] [PMID: 27570871]
[2]
Scheltens P, Blennow K, Breteler MM, et al. Alzheimer’s disease. Lancet 2016; 388(10043): 505-17.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[3]
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011; 70(11): 960-9.
[http://dx.doi.org/10.1097/NEN.0b013e318232a379] [PMID: 22002422]
[4]
Schellenberg GD, Montine TJ. The genetics and neuropathology of Alzheimer’s disease. Acta Neuropathol 2012; 124(3): 305-23.
[http://dx.doi.org/10.1007/s00401-012-0996-2] [PMID: 22618995]
[5]
Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet 2017; 390(10113): 2673-734.
[http://dx.doi.org/10.1016/S0140-6736(17)31363-6] [PMID: 28735855]
[6]
Kunkle BW, Grenier-Boley B, Sims R, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet 2019; 51(3): 414-30.
[http://dx.doi.org/10.1038/s41588-019-0358-2] [PMID: 30820047]
[7]
Jansen IE, Savage JE, Watanabe K, et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat Genet 2019; 51(3): 404-13.
[http://dx.doi.org/10.1038/s41588-018-0311-9] [PMID: 30617256]
[8]
Zhou X, Chen Y, Mok KY, et al. Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis. Proc Natl Acad Sci USA 2018; 115(8): 1697-706.
[http://dx.doi.org/10.1073/pnas.1715554115] [PMID: 29432188]
[9]
Andrews SJ, Fulton-Howard B, Goate A. Interpretation of risk loci from genome-wide association studies of Alzheimer’s disease. Lancet Neurol 2020; 19(4): 326-35.
[http://dx.doi.org/10.1016/S1474-4422(19)30435-1] [PMID: 31986256]
[10]
Mez J, Chung J, Jun G, et al. Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans. Alzheimers Dement 2017; 13(2): 119-29.
[http://dx.doi.org/10.1016/j.jalz.2016.09.002] [PMID: 27770636]
[11]
Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92(8): 827-39.
[http://dx.doi.org/10.1161/01.RES.0000070112.80711.3D] [PMID: 12730128]
[12]
Montagne A, Nation DA, Sagare AP, et al. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. Nature 2020; 581(7806): 71-6.
[http://dx.doi.org/10.1038/s41586-020-2247-3] [PMID: 32376954]
[13]
Saha P, Sarkar S, Paidi RK, Biswas SC. TIMP-1: A key cytokine released from activated astrocytes protects neurons and ameliorates cognitive behaviours in a rodent model of Alzheimer’s disease. Brain Behav Immun 2020; 87: 804-19.
[http://dx.doi.org/10.1016/j.bbi.2020.03.014] [PMID: 32194232]
[14]
Stomrud E, Björkqvist M, Janciauskiene S, Minthon L, Hansson O. Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer’s disease. Alzheimers Res Ther 2010; 2(3): 20.
[http://dx.doi.org/10.1186/alzrt44] [PMID: 20576109]
[15]
Gremer L, Schölzel D, Schenk C, et al. Fibril structure of amyloid-β(1-42) by cryo-electron microscopy. Science 2017; 358(6359): 116-9.
[http://dx.doi.org/10.1126/science.aao2825] [PMID: 28882996]
[16]
Schultz N, Nielsen HM, Minthon L, Wennström M. Involvement of matrix metalloproteinase-9 in amyloid-β 1-42-induced shedding of the pericyte proteoglycan NG2. J Neuropathol Exp Neurol 2014; 73(7): 684-92.
[http://dx.doi.org/10.1097/NEN.0000000000000084] [PMID: 24918635]
[17]
Yan P, Hu X, Song H, et al. Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J Biol Chem 2006; 281(34): 24566-74.
[http://dx.doi.org/10.1074/jbc.M602440200] [PMID: 16787929]
[18]
Hernandez-Guillamon M, Mawhirt S, Blais S, et al. Sequential amyloid-β degradation by the matrix metalloproteases MMP-2 and MMP-9. J Biol Chem 2015; 290(24): 15078-91.
[http://dx.doi.org/10.1074/jbc.M114.610931] [PMID: 25897080]
[19]
Nübling G, Levin J, Bader B, et al. Limited cleavage of tau with matrix-metalloproteinase MMP-9, but not MMP-3, enhances tau oligomer formation. Exp Neurol 2012; 237(2): 470-6.
[http://dx.doi.org/10.1016/j.expneurol.2012.07.018] [PMID: 22890115]
[20]
Terni B, Ferrer I. Abnormal expression and distribution of MMP2 at initial stages of Alzheimer’s disease-related pathology. J Alzheimers Dis 2015; 46(2): 461-9.
[http://dx.doi.org/10.3233/JAD-142460] [PMID: 26402409]
[21]
Ho WM, Chen CM, Lee YS, et al. Association of MMP-9 haplotypes and TIMP-1 polymorphism with spontaneous deep intracerebral hemorrhage in the Taiwan population. PLoS One 2015; 10(5): e0125397.
[http://dx.doi.org/10.1371/journal.pone.0125397] [PMID: 25932641]
[22]
Chen YC, Ho WM, Lee YS, Chen HW, Chen CM. Polymorphisms in the promoters of the MMP-2 and TIMP-2 genes are associated with spontaneous deep intracerebral hemorrhage in the Taiwan population. PLoS One 2015; 10(11): e0142482.
[http://dx.doi.org/10.1371/journal.pone.0142482] [PMID: 26551785]
[23]
Chen YC, Wu YR, Mesri M, Chen CM. Associations of matrix metalloproteinase-9 and tissue inhibitory factor-1 polymorphisms with Parkinson disease in Taiwan. Medicine (Baltimore) 2016; 95(5): e2672.
[http://dx.doi.org/10.1097/MD.0000000000002672] [PMID: 26844501]
[24]
Tuna G, Yener GG, Oktay G, İşlekel GH, Kİrkalİ FG. Evaluation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in plasma from patients with neurodegenerative dementia. J Alzheimers Dis 2018; 66(3): 1265-73.
[http://dx.doi.org/10.3233/JAD-180752] [PMID: 30412498]
[25]
Chen CH, Yang JH, Chiang CWK, et al. Population structure of Han Chinese in the modern Taiwanese population based on 10,000 participants in the Taiwan Biobank project. Hum Mol Genet 2016; 25(24): 5321-31.
[http://dx.doi.org/10.1093/hmg/ddw346] [PMID: 27798100]
[26]
Fan CT, Hung TH, Yeh CK. Taiwan regulation of biobanks. J Law Med Ethics 2015; 43(4): 816-26.
[http://dx.doi.org/10.1111/jlme.12322] [PMID: 26711420]
[27]
Wei CY, Yang JH, Yeh EC, et al. Genetic profiles of 103,106 individuals in the Taiwan Biobank provide insights into the health and history of Han Chinese. NPJ Genom Med 2021; 6(1): 10.
[http://dx.doi.org/10.1038/s41525-021-00178-9] [PMID: 33574314]
[28]
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15(7): 539-53.
[http://dx.doi.org/10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S] [PMID: 9686693]
[29]
Schoenborn CA, Adams PE. Health behaviors of adults: United States, 2005-2007. Vital Health Stat 10 2010; (245): 1-132.
[PMID: 20669609]
[30]
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[31]
Qin H, Sun Y, Benveniste EN. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 1999; 274(41): 29130-7.
[http://dx.doi.org/10.1074/jbc.274.41.29130] [PMID: 10506168]
[32]
Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21(2): 263-5.
[http://dx.doi.org/10.1093/bioinformatics/bth457] [PMID: 15297300]
[33]
Reuter B, Bugert P, Stroick M, et al. TIMP-2 gene polymorphism is associated with intracerebral hemorrhage. Cerebrovasc Dis 2009; 28(6): 558-63.
[http://dx.doi.org/10.1159/000247599] [PMID: 19844095]
[34]
Chang KP, Hao SP, Liu CT, et al. Promoter polymorphisms of DNMT3B and the risk of head and neck squamous cell carcinoma in Taiwan: a case-control study. Oral Oncol 2007; 43(4): 345-51.
[http://dx.doi.org/10.1016/j.oraloncology.2006.04.006] [PMID: 16920385]
[35]
González JR, Armengol L, Solé X, et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics 2007; 23(5): 644-5.
[http://dx.doi.org/10.1093/bioinformatics/btm025] [PMID: 17267436]
[36]
Gauderman WJ. Sample size requirements for association studies of gene-gene interaction. Am J Epidemiol 2002; 155(5): 478-84.
[http://dx.doi.org/10.1093/aje/155.5.478] [PMID: 11867360]
[37]
Murphy G. Tissue inhibitors of metalloproteinases. Genome Biol 2011; 12(11): 233-33.
[http://dx.doi.org/10.1186/gb-2011-12-11-233] [PMID: 22078297]
[38]
Eckfeld C, Häußler D, Schoeps B, Hermann CD, Krüger A. Functional disparities within the TIMP family in cancer: hints from molecular divergence. Cancer Metastasis Rev 2019; 38(3): 469-81.
[http://dx.doi.org/10.1007/s10555-019-09812-6] [PMID: 31529339]
[39]
Lorenzl S, Albers DS, LeWitt PA, et al. Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases. J Neurol Sci 2003; 207(1-2): 71-6.
[http://dx.doi.org/10.1016/S0022-510X(02)00398-2] [PMID: 12614934]
[40]
Hanzel CE, Iulita MF, Eyjolfsdottir H, et al. Analysis of matrix metallo-proteases and the plasminogen system in mild cognitive impairment and Alzheimer’s disease cerebrospinal fluid. J Alzheimers Dis 2014; 40(3): 667-78.
[http://dx.doi.org/10.3233/JAD-132282] [PMID: 24531161]
[41]
Mroczko B, Groblewska M, Zboch M, et al. Concentrations of matrix metalloproteinases and their tissue inhibitors in the cerebrospinal fluid of patients with Alzheimer’s disease. J Alzheimers Dis 2014; 40(2): 351-7.
[http://dx.doi.org/10.3233/JAD-131634] [PMID: 24448781]
[42]
Duits FH, Hernandez-Guillamon M, Montaner J, et al. Matrix Metalloproteinases in Alzheimer’s Disease and Concurrent Cerebral Microbleeds. J Alzheimers Dis 2015; 48(3): 711-20.
[http://dx.doi.org/10.3233/JAD-143186] [PMID: 26402072]
[43]
Hernández-Guillamon M, Delgado P, Ortega L, et al. Neuronal TIMP-1 release accompanies astrocytic MMP-9 secretion and enhances astrocyte proliferation induced by beta-amyloid 25-35 fragment. J Neurosci Res 2009; 87(9): 2115-25.
[http://dx.doi.org/10.1002/jnr.22034] [PMID: 19235898]
[44]
Dafnis I, Tzinia AK, Tsilibary EC, Zannis VI, Chroni A. An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines. Neuroscience 2012; 210: 21-32.
[http://dx.doi.org/10.1016/j.neuroscience.2012.03.013] [PMID: 22445724]

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