Association analysis between K and −116A variants of butyrylcholinesterase and Alzheimer’s disease in a Brazilian population

Simão-Silva, Daiane Priscila; Bertolucci, Paulo Henrique Ferreira; Lábio, Roger Willian de; Payão, Spencer Luíz Marques; Furtado-Alle, Lupe; Souza, Ricardo Lehtonen Rodrigues de

doi:10.1016/j.cbi.2012.09.008

Cited by 8 publications

(7 citation statements)

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“…Thus, this variant may pose either a risk or a protective factor in AD (Podoly et al, 2009). This study found no association between the K variant and AD, similar to the study of Simão- Silva et al (2013) in a southeastern Brazilian population. The debate of the BChE function on AD neuropathology was accompanied by several studies that aimed to verify association between BChE-K and Alzheimer's disease.…”

Section: Discussionsupporting

confidence: 89%

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Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population

Bono

Simão-Silva

Batistela

et al. 2015

Neurochemistry International

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Alzheimer's disease (AD) is a neurodegenerative disorder in which there is a decline of cholinergic function. The symptomatic AD treatment involves the use of ChEIs (cholinesterase inhibitors) as rivastigimine, a dual inhibitor. The human butyrylcholinesterase (BChE) is an enzyme that has specific roles in cholinergic neurotransmission and it has been associated with AD. In the serum, BChE is found in four main molecular forms: G1 (monomer); G1-ALB (monomer linked to albumin); G2 (dimer); and G4 (tetramer). The interaction between the products of BCHE gene and CHE2 locus results in CHE2 C5+ and CHE2 C5- phenotypes. CHE2 C5+ phenotype and BChE-K are factors that influence on BChE activity. This work aimed to verify the proportions of BChE molecular forms, total and relative activity in 139 AD patients and 139 elderly controls, taking into account K variant, CHE2 locus, rivastigmine treatment and clinical dementia rating (CDR) of AD patients. Phenotypic frequencies of CHE2 C5+ and frequency of the carriers of the K allele were similar between groups. Total BChE activity in plasma was significantly lower in AD patients than in elderly controls. Furthermore, we found that reduction on plasma BChE activity is associated directly with AD progression in AD patients and that rivastigmine treatment has a stronger effect on BChE activity within the CDR2 group. The reduction in BChE activity did not occur proportionally in all molecular forms. Multiple regression analysis results confirmed that AD acts as the main factor in plasma BChE activity reduction and that severe stages are related with an even greater reduction. These findings suggest that the reduction of total plasma BChE and relative BChE molecular forms activity in AD patients is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic secondary marker for AD.

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Section: Discussionsupporting

confidence: 89%

“…DNA extraction was performed by a salting-out method (Lahiri and Nurnberger, 1991) and then diluted to a final concentration of 20 ng/μL. Genotyping of K variant (rs1803274) was obtained by TaqMan SNP Genotyping Assay produced by Life Technologies according to Simão-Silva et al (2013).…”

Section: Laboratory Analysismentioning

confidence: 99%

Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population

Bono

Simão-Silva

Batistela

et al. 2015

Neurochemistry International

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“…A total of 25 eligible case-control studies (3850 cases and 3947 controls) met the inclusion criteria [ 8 – 32 ]. Among these 25 case-control studies, 5 studies focused on Asians and 20 focused on Caucasians.…”

Section: Resultsmentioning

confidence: 99%

“…This polymorphism is associated with a 30% reduction of serum BCHE activity [ 7 ]. Many studies have been conducted to evaluate the association between BCHE K variant and AD risk [ 8 – 32 ]. However, the results are controversial and inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Butyrylcholinesterase K Variant and Alzheimer’s Disease Risk: A Meta-Analysis

et al. 2015

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BackgroundAlthough many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer’s disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis.Material/MethodsWe searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association.ResultsWe found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03–1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02–1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95–1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05–1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89–1.51; P=0.27). Compared with non-APOE ɛ4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91–1.35; P=0.30). However, APOE ɛ4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75–4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82–6.02; P=0.0001).ConclusionsThe results of this meta-analysis indicate that BCHE K variant might be associated with AD risk.

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“…For BDNF C270T, there have been four positive results in Europeans (13,17) and Asians (18,19) and 14 negative results in Europeans (28)(29)(30)(31)(34)(35)(36)(37)(43)(44)(45), Asians (40,41) and Africans (29). For BCHE-K variants, there have been six positive results in Europeans (46-51) and 22 negative results in Europeans (5,(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67) and Asians (68)(69)(70)(71)(72). Discrepancies among the previous association studies may have been the result of limited power, different ethnic backgrounds or the different processes and status in patients with AD.…”

Section: Introductionmentioning

confidence: 99%

Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls

Dai

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with β-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date.

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Association analysis between K and −116A variants of butyrylcholinesterase and Alzheimer’s disease in a Brazilian population

Cited by 8 publications

References 25 publications

Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population

Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population

Butyrylcholinesterase K Variant and Alzheimer’s Disease Risk: A Meta-Analysis

Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls

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