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

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.

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

“…HSPG2 is expressed in basement membranes in several tissues, including brain. 55 It has been previously associated with Alzheimer's disease 56 and intracranial aneurysms. 57 As suggested by Syu et al, 30 its involvement in TD pathophysiology may be related to its influence on cholinergic transmission.…”

<i>HSPG2</i> Gene C/A Polymorphism Does Not Confer Susceptibility to Alzheimer’s Disease in Chinese

“…The allelic distributions (39% for allele C) in our control sample differed markedly from Finnish and Jewish populations (76 and 15.3%, respectively) and reveal ethnic differences [17,18] . Despite ethnic differences, our significant negative association of the polymorphism alone with AD is consistent with those two reports [17,18] . Our finding reinforces the notion that the HSPG2 polymorphism does not confer major genetic risk for AD in different ethnic groups.…”

“…HSPG2 allele A was detected to increase the risk for AD in APOE 4 carriers with doubled odds ratio (OR) in Finnish subjects [17] . But the study in Jewish populations has failed to find a significant association of the polymorphism with LOAD [18] .…”

“…Recently, the association between a common Bam H I polymorphism C/A in intron 6 of HSPG2 and AD was analyzed by two groups within Finnish and Jewish populations, respectively [17,18] . HSPG2 allele A was detected to increase the risk for AD in APOE 4 carriers with doubled odds ratio (OR) in Finnish subjects [17] .…”

Endostatin and endorepellin: A common route of action for similar angiostatic cancer avengers

“…Originally perlecan was isolated from the basement membrane of Engelbreth-Holm-Swarm (EHS) mouse sarcoma revealing a molecule that was first hypothesized to function as an anionic filter, but later described as the multimeric proteoglycan perlecan [117]. The HSPG2 gene is located on chromosome 1p36, and is composed of 97 exons, covering over 120 kb of DNA [118, 119]. It possesses a complex structure organized in an array of five bioactive modules with high homology to a multitude of adhesion and signaling proteins, and growth factors, accounting for its broad biological activity [110].…”