Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease
Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease
复制标题
DOI：
10.1097/00041444-200209000-00006
复制
发表时间：
2002-09-01
影响因子：
0.9
通讯作者：
Nitsch, RM
中科院分区：
文献类型：
--
作者：
Wollmer, MA;Papassotiropoulos, A;Nitsch, RM
金属蛋白酶 I 组织抑制剂 (TIMP-1) 可抑制多种蛋白酶，包括解整合素和金属蛋白酶 10 (ADAM10)，这是一种主要的 α 分泌酶，可在其淀粉样蛋白形成 Abeta 结构域内裂解 β-淀粉样蛋白前体蛋白。编码 TIMP-1 (TIMP1) 的基因定位于 X 染色体的短臂，该区域先前被认为赋予阿尔茨海默病 (AD) 的遗传易感性。为了确定 TIMP1 的遗传变异是否与 AD 的发病机制有关，我们分析了来自两个独立且不同种族群体的 AD 患者和对照受试者的 TIMP1 内的一种单核苷酸多态性和 TIMP1 5'-非翻译区的一种单核苷酸多态性。我们没有观察到 TIMP1 基因型与男性或女性 AD 诊断之间存在任何关联。我们还测量了 AD 患者、健康对照受试者和其他神经系统疾病患者脑脊液中 TIMP-1 蛋白水平。所有组中的 TIMP-1 水平相似。此外，TIMP1 基因型分层后未观察到显着差异。我们的数据表明，遗传变异性和 TIMP-1 蛋白水平均与 AD 无关。 (C) 2002 年利平科特·威廉姆斯·威尔金斯。
Tissue inhibitor of metalloproteinases I (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-I levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD. (C) 2002 Lippincott Williams Wilkins.