Association of BACE1 Gene Polymorphism with Alzheimer’s Disease in Asian Populations: Meta-Analysis Including Korean Samples

Abstract

Background: β-Site amyloid precursor protein cleaving enzyme (BACE) is a candidate risk factor for Alzheimer’s disease (AD) from its key role in β-amyloid generation. Previous genetic association studies of BACE1 gene have yielded conflicting results. This study is an attempt to clarify whether the common SNP in exon 5 of BACE1 (rs638405, Val262) is associated with a risk for late-onset AD. Methods: We genotyped a synonymous C/G polymorphism of BACE1 located in exon 5 and apolipoprotein E (ApoE) in 248 AD patients and 224 healthy persons. A meta-analysis with pooled data from four Chinese studies and our results was performed. Results: The allele and genotype frequencies of BACE1 polymorphism were not significantly different between cases and controls (p > 0.05) in the Korean population. A meta-analysis of previously published Asian populations including Koreans showed evidence of a weak association (p = 0.0555 for genotypes, p = 0.0352 for alleles). However, a significant association between the CC genotype and AD was observed in the ApoE-Ε4-positive groups (p = 0.0044, OR = 1.995; 95% CI = 1.319–3.018). Conclusion: These data suggest that BACE1 polymorphism in exon 5 influences risk for late-onset AD in those carrying the ApoE Ε4 allele.

Promoter polymorphisms which modulate BACE1 expression are associated with sporadic Alzheimer's disease

“…We failed to find any association between the exon 5 C/G polymorphism and SAD even after statistical adjustment for age, gender and APOE e4 allele status. Our results were in agreement with two recent studies [Jo et al, 2008;Todd et al, 2008]. LD between the promoter polymorphisms and the exon 5 C/G polymorphism was also analyzed.…”

Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease

“…Mutation of these genes showed a common phenomenon of an increase of Aβ 1-42 or of the ratio of Aβ 1-42 to Aβ 1-40 ; Aβ 1-42 is more hydrophobic and more prone to aggregate than Aβ 1-40 (Jarrett et al ., 1993). Furthermore, we also found in Asian population including Korean that beta-site APP cleaving enzyme (BACE)-1 polymorphism in exon 5 infl uences a risk for LOAD in those carrying the ApoE ε4 allele (Jo et al ., 2008) although Caucasian may not be the case. These observations strongly suggest a cause-and-effect relationship between Aβ accumulation and AD pathogenesis.…”

Facilitation of glutamate, but not GABA, release in Familial Alzheimer's APP mutant Knock‐in rats with increased β‐cleavage of APP

“…Mutations in APP and in genes that regulate APP processing—such as PSEN1 / PSEN2 , γ‐secretase components, and BRI2/ ITM2B —cause familial dementia (De Strooper & Voet, ; Garringer, Murrell, D'Adamio, Ghetti & Vidal, ; Giliberto, Matsuda, Vidal & D'Adamio, ; Matsuda, Giliberto, Matsuda, McGowan & D'Adamio, ; Matsuda, Matsuda, Snapp & D'Adamio, ; Matsuda, Tamayev & D'Adamio, ; Matsuda et al., ; Tamayev, Matsuda, Arancio & D'Adamio, ; Tamayev, Matsuda, Fa, Arancio & D'Adamio, ; Tamayev, Matsuda, Giliberto, Arancio & D'Adamio, ; Tamayev, Giliberto et al., ). BACE1 gene polymorphisms as well as increased BACE1 expression/activity are associated with sporadic dementia (Cheng et al., ; Hampel & Shen, ; Hebert et al., ; Holsinger, Lee, Boyd, Masters & Collins, ; Jo et al., ; Kan et al., ; Long, Ray & Lahiri, ). In contrast, humans carrying the Icelandic APP variant, which codes for an APP protein that is inefficiently cleaved by BACE1, are protected from dementia and normal cognitive decline (Jonsson et al., ).…”