Meta-analysis of genetic variability in the ?-amyloid production, aggregation and degradation metabolic pathways and the risk of Alzheimer?s disease

Llorca, Javier; Rodríguez-Rodríguez, Eloy; Dierssen-Sotos, Trinidad; Delgado-Rodrı́guez, Miguel; Berciano, José; Combarros, Onofre

doi:10.1111/j.1600-0404.2007.00899.x

Cited by 13 publications

(14 citation statements)

References 87 publications

(196 reference statements)

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“…The distribution of genotypes for the two polymorphisms did not diverge from the Hardy-Weinberg equilibrium ( Table 2). The frequencies of the BLMH genotypes in the all groups were similar to those previously reported in the literature [18]. There were no significant differences in APOE genotypes or allele distributions between groups ( Table 2); however, the genotype 3/3 was most frequent for all subjects (61.1%).…”

Section: Resultssupporting

confidence: 87%

“…Previous studies investigating BLMH 1450 G > A in AD and control subjects have found that subjects with the G/G alleles and without APOE allele 4 had four times greater likelihood to have AD [23][24][25]. However, this association between BLMH genotypes and AD was not found by other researchers [18,[26][27][28]. The relationship between BLMH expression and Val443Ill isoforms with amount of patients bigger than our study, it still is an alternative for another researchinasmuch as the 1450 G > A covers the BH's active and it can have an influence about the disease.…”

Section: Discussionmentioning

confidence: 79%

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BLMH and APOE genes in Alzheimer Disease: A possible relation

Ximenez¹,

Rasmussen²,

Orcini³

et al. 2013

AAD

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Alzheimer disease (AD) is a progressive and irreversible neurodegenerative disorder that is characterized by cognitive decline, memory loss and confusion. The E4 allele of the apolipoprotein E gene (APOE) is associated with AD and it is the main genetic risk factor for disease. Although the exact physiological function is unknown, bleomycin hydrolase (BLMH) may also be associated with AD development, although previous immunohistochemical findings have been inconsistent. Therefore, the purpose of this study was to evaluate the genotypic and allele frequencies of the APOE gene and BLMH 1450 G > A polymorphism and assess BLMH expression using PCR-RFLP and RT-qPCR analyses of blood samples from patients with Alzheimer disease (AD), healthy elderly adults (EC) and healthy young subjects (YC). BLMH expression was significantly different among groups (p = 0.015) and there was substantial reduction with age and with AD. The APOE and BLMH genotype frequency did not diverge from the Hardy-Weinberg equilibrium. There was a higher frequency of genotype 3/3 in all subjects (61.1%) and the AD group demonstrated a higher frequency of allele 4; however, differences in genotype and allele distributions were statistically different among groups.

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Section: Resultssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 79%

BLMH and APOE genes in Alzheimer Disease: A possible relation

Ximenez¹,

Rasmussen²,

Orcini³

et al. 2013

AAD

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“…In addition a meta-analysis of the available data does not support a link between genetic variations in CYP46A1 and the risk of AD (Llorca et al, 2008).…”

Section: Introductionmentioning

confidence: 86%

A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations

et al. 2010

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Pages: 25 Pages including 2 tables Abstract:2 Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism were not associated with AD (OR=1.03; 95% CI=0.72-1.48). However, we did find evidence supporting an interaction between the HMGCR A allele, the APOE E4 allele and an altered risk of AD (OR=2.41; 95% CI=0.93-6.22).

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“…A significant association between the rs638405 GG genotype and AD was noted [6]. This study has been replicated by several research teams, although some found contrasting results [7]. …”

Section: Introductionmentioning

confidence: 62%

Association of BACE1 Gene Polymorphism with Cerebellar Volume but Not Cognitive Function in Normal Individuals

Tsai

Huang²,

Yang

et al. 2012

Dement Geriatr Cogn Disord Extra

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Aims: β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a biological and positional candidate gene for Alzheimer’s disease (AD). Previous studies found that BACE1-null mice had impaired performance on cognition and neurodegeneration during the aging process. Additionally, a synonymous polymorphism of BACE1 (rs638405) in exon 5 has been reported to be associated with risk for AD. We hypothesized that this BACE1 gene variant might influence regional brain volumes and cognitive tests in normal individuals. Methods: Participants were 330 normal volunteers between 21 and 92 years of age (mean age 56.3 ± 22.0 years; 191 males, 139 females). Cognitive tests (the Mini-Mental State Examination and Digit Spans), magnetic resonance imaging, and genotyping of BACE1 rs638405 were examined for each subject. The differences in regional gray matter (GM) volumes between G homozygotes and C-allele carriers were tested using optimized voxel-based morphometry. Results: Compared to C-allele carriers, G homozygotes exhibited significantly larger GM volumes in the left cerebellar culmen and right cerebellar lingual area, but no significant differences on cognitive function tests. Conclusion: The findings suggest that the BACE1 rs638405 polymorphism may affect cerebellar morphology, but not cognitive function in healthy humans.

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Meta-analysis of genetic variability in the ?-amyloid production, aggregation and degradation metabolic pathways and the risk of Alzheimer?s disease

Abstract: The overall impact on AD risk of the genes for which meta-analyses are now available is rather limited. Additional meta-analyses of other different genes encoding for A beta production, aggregation and degradation mediators might help in determining the risk profile for AD.

Cited by 13 publications

References 87 publications

BLMH and APOE genes in Alzheimer Disease: A possible relation

BLMH and APOE genes in Alzheimer Disease: A possible relation

A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations

Association of BACE1 Gene Polymorphism with Cerebellar Volume but Not Cognitive Function in Normal Individuals

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