硫酸乙酰肝素蛋白聚糖基因（基底膜聚糖，HSPG2）多态性与阿尔茨海默病的关联研究。

An association study of a polymorphism in the heparan sulfate proteoglycan gene (perlecan, HSPG2) and Alzheimer's disease.

作者信息

Rosenmann Hanna, Meiner Zeev, Kahana Esther, Aladjem Zoja, Friedman Gideon, Ben-Yehuda Arie, Grenader Tal, Wertman Eli, Abramsky Oded

机构信息

Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem 91120, Israel.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):123-5. doi: 10.1002/ajmg.b.30015.

DOI:10.1002/ajmg.b.30015

PMID:15211644

Abstract

Accumulating evidence indicates that the heparan-sulfate-proteoglycan (perlecan, HSPG2), as well as other specific proteoglycans, are involved in amyloidogenesis and tau aggregation in Alzheimer's disease (AD). Moreover, the HSPG2 is located on chromosome 1p36, a region of linkage to late-onset AD (LOAD). These two criteria, pathological and positional, make the HSPG2 an interesting candidate for an association with AD. We performed a case-control association study between the common intron 6 BamHI polymorphism at a region of putative heparan-sulfate (HS) attachment sites in the HSPG2 gene and sporadic AD in Jews. No association was detected with AD, neither as a risk factor nor as a modifier gene affecting the age at disease onset and disease progression. In addition, no interactive effect was found with the known risk factor for AD, the apolipoprotein E (APOE) epsilon4. These findings show no evidence for association between HSPG2 intron 6 BamHI polymorphism and AD in our population.

摘要

越来越多的证据表明，硫酸乙酰肝素蛋白聚糖（基底膜聚糖，HSPG2）以及其他特定的蛋白聚糖，参与了阿尔茨海默病（AD）中的淀粉样蛋白生成和tau蛋白聚集。此外，HSPG2位于1p36染色体上，该区域与晚发性AD（LOAD）存在连锁关系。病理和定位这两个标准，使得HSPG2成为与AD关联的一个有趣候选基因。我们在HSPG2基因中假定的硫酸乙酰肝素（HS）附着位点区域的常见内含子6 BamHI多态性与犹太人散发性AD之间进行了病例对照关联研究。未检测到与AD的关联，既未作为危险因素，也未作为影响发病年龄和疾病进展的修饰基因。此外，未发现与已知的AD危险因素载脂蛋白E（APOE）ε4存在交互作用。这些发现表明，在我们的人群中，没有证据支持HSPG2内含子6 BamHI多态性与AD之间存在关联。