de Souza RLR


Full name : de Souza Ricardo LLehtonen R

First name : Ricardo LehtonenR

Mail : Federal University of Paran\; Genetics\; PO Box 19071\; Curitiba\; 81531

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Country : Brazil

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Phone : +554133611554

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References (32)

Title : Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders - Furtado-Alle_2023_Chem.Biol.Interact_14ChEPon_110680
Author(s) : Furtado-Alle L , Turek LV , de Oliveira CS , Hortega JVM , de Souza RLR
Ref : Chemico-Biological Interactions , :110680 , 2023
Abstract : Butyrylcholinesterase (BChE), an enzyme primarily found in the liver, plasma, and brain, has been recognized for its role in the hydrolysis of choline esters. Recent studies have shed light on its involvement in lipid metabolism, revealing its potential as a crucial player in maintaining lipid homeostasis. However, the interactions between external factors and BChE activity in lipid metabolic pathways remain a complex subject of study. This review summarizes the current knowledge regarding BChE activity and lipid metabolism and seeks to clarify the nature of this relationship as causal or consequential. Evidence supports the role of BChE in energy homeostasis disruption, such as obesity and related metabolic disorders, where it exhibits lipolytic activity and mediates fatty acid use and storage. The unexpected functions of BChE in lipoprotein synthesis and the impact of polymorphic variants of the BCHE gene suggest a central role in lipid metabolism; however, further investigation is needed to confirm and describe these functions, especially considering the metabolic context. Furthermore, exploring therapeutic interventions in lipid metabolism disorders contributes to elucidating their implications on BChE activity, but attention to the metabolic status and genotypes as possible factors in this interaction is needed. In summary, further research in this field holds promise for improving our understanding of the complex interplay between BChE and lipid metabolism, and its potential clinical applications. However, the available data corroborate the dual role of BChE activity, both as a critical responsive element to metabolic challenges and as a predisposition factor to metabolic diseases.
ESTHER : Furtado-Alle_2023_Chem.Biol.Interact_14ChEPon_110680
PubMedSearch : Furtado-Alle_2023_Chem.Biol.Interact_14ChEPon_110680
PubMedID: 37634560

Title : BChE inhibitors from marine organisms - A review - Lins_2022_Chem.Biol.Interact__110136
Author(s) : Lins Alves LK , Cechinel Filho V , de Souza RLR , Furtado-Alle L
Ref : Chemico-Biological Interactions , :110136 , 2022
Abstract : Acetylcholine is a key neurotransmitter for brain and muscle function, that has its levels decreased in the brain of people with Alzheimer's Disease (AD). Cholinesterase inhibitors are medicines that decrease the breakdown of acetylcholine, through the inhibition of acetyl- and butyrylcholinesterase enzymes. Despite the fact that butyrylcholinesterase activity rises with the disease, while acetylcholinesterase activity declines, the cholinesterase inhibitors that are currently commercialized inhibit either acetylcholinesterase or both enzymes. The development of selective butyrylcholinesterase inhibitors is a promising strategy in the search for new drugs acting against AD. The marine environment is a rich source of molecules with therapeutic potential, which can provide compounds more easily than traditional methods, with reduced toxicity risks compared to synthetic molecules. This review comprises articles from 2003 to 2020, that assessed the butyrylcholinesterase inhibitory activities from marine organisms, considering their crude extracts and isolated compounds. Part of the articles reported a multi-target activity, inhibiting also other AD-related enzymes. Some of the marine compounds reported here have shown an excellent potential for butyrylcholinesterase inhibition compared to standard inhibitors. Further studies of some compounds reported here may lead to the development of a new treatment for AD.
ESTHER : Lins_2022_Chem.Biol.Interact__110136
PubMedSearch : Lins_2022_Chem.Biol.Interact__110136
PubMedID: 36096160

Title : Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in women - Oliveira_2017_Genet.Mol.Biol__0
Author(s) : Oliveira J , Tureck LV , Santos WD , Saliba LF , Schenknecht CS , Scaraboto D , de Souza RLR , Furtado-Alle L
Ref : Genet Mol Biol , :0 , 2017
Abstract : Butyrylcholinesterase (BChE) activity and polymorphisms in its encoding gene had previously been associated with metabolic traits of obesity. This study investigated the association of three single nucleotide polymorphisms (SNPs) in the BCHE gene: -116G > A (rs1126680), 1615GA (rs1803274), 1914A < G (rs3495), with obesity and lipid metabolism markers, body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG) levels, and BChE enzymatic activity in obese (BMI>/=30/n = 226) and non-obese women (BMI < 25/n = 81). BCHE SNPs genotyping was obtained by TaqMan allelic discrimination assay and by RFLP-PCR. Plasmatic BChE activity was measured using propionylthiocholine as substrate. Similar allele frequencies were found in obese and non-obese women for the three studied SNPs (p > 0.05). The dominant and recessive models were tested, and different effects were found. The -116A allele showed a dominant effect in BChE activity reduction in both non-obese and obese women (p = 0.045 and p < 0.001, respectively). The 1914A > G and 1615GA SNPs influenced the TG levels only in obese women. The 1914G and the 1615A alleles were associated with decreased plasma levels of TG. Thus, our results suggest that the obesity condition, characterized by loss of energy homeostasis, is modulated by BCHE polymorphisms.
ESTHER : Oliveira_2017_Genet.Mol.Biol__0
PubMedSearch : Oliveira_2017_Genet.Mol.Biol__0
PubMedID: 28497838

Title : Plasma butyrylcholinesterase activity: a possible biomarker for differential diagnosis between Alzheimer's disease and dementia with Lewy bodies? - Josviak_2017_Int.J.Neurosci__1
Author(s) : Josviak ND , Batistela MS , Souza RKM , Wegner NR , Bono GF , Sulzbach CD , Simao-Silva DP , Piovezan MR , de Souza RLR , Furtado-Alle L
Ref : International Journal of Neuroscience , :1 , 2017
Abstract : Butyrylcholinesterase (BChE) is an enzyme encoded by BCHE gene, responsible for catalyzing the hydrolysis of acetylcholine. K and -116A BCHE variants were associated with decrease in plasma BChE activity, and their influence has been investigated in diseases with a cholinergic deficit such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). In order to check the influence of BCHE genetic variants on enzymatic activity, all patients and controls were genotyped for K and -116A variants. We found lower plasma BChE activity in DLB patients compared to elderly controls and to AD independent of the presence of K or -116A variants. Our results suggest that the reduction of total plasma BChE activity is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic marker for differential diagnosis between AD and DLB.
ESTHER : Josviak_2017_Int.J.Neurosci__1
PubMedSearch : Josviak_2017_Int.J.Neurosci__1
PubMedID: 28504037

Title : Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study - Santos_2017_Arch.Endocrinol.Metab__0
Author(s) : Santos WD , Tureck LV , Saliba LF , Schenknecht CS , Scaraboto D , de Souza RLR , Furtado-Alle L
Ref : Arch Endocrinol Metab , :0 , 2017
Abstract : Objective: Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. Subjects and methods: One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. Results: The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. Conclusion: In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.
ESTHER : Santos_2017_Arch.Endocrinol.Metab__0
PubMedSearch : Santos_2017_Arch.Endocrinol.Metab__0
PubMedID: 28658346

Title : Association between RAPH1 Gene Haplotypes and CHE2 Locus Phenotypes - De Andrade_2016_Ann.Hum.Genet_80_203
Author(s) : de Andrade FA , Batistela MS , Amaral Sda C , Dos Santos W , Mikami LR , Chautard-Freire-Maia EA , Furtado-Alle L , de Souza RLR
Ref : Ann Hum Genet , 80 :203 , 2016
Abstract : The human butyrylcholinesterase (BChE) is a serum esterase that has been associated with body mass index (BMI) and obesity. Its activity is conditioned by alleles of BCHE gene and the CHE2 locus that codifies an unknown BChE-binding protein (C5 complex). The hypothesis that the CHE2 locus is the RAPH1 gene, which encodes lamellipodin (Lpd), was raised in a study that observed Lpd peptides released from denatured BChE tetramers. The aim of this study was to test this hypothesis by evaluating SNPs of RAPH1 gene (rs2246118:C > T, rs3814365:A > G and rs2465520:C > T) in 34 CHE2 C5+ and 92 CHE2 C5- individuals, corresponding to the presence and absence of C5 complex. The results showed association of two haplotypes (CAC and TGC) with CHE2 C5+ phenotype. RAPH1 haplotypes was also associated with intense (TGC) and faint (CAC) CHE2 C5+ phenotypes. BChE activity was higher in intense CHE2 C5+ than faint CHE2 C5+ phenotype. Our results corroborate the hypothesis that the RAPH1 gene is the CHE2 locus and suggest that the variable expressivity of the CHE2 C5+ phenotypes is, at least in part, due to its genetic heterogeneity, which is leading to increased BChE activity only in individuals with intense CHE2 C5+ phenotype.
ESTHER : De Andrade_2016_Ann.Hum.Genet_80_203
PubMedSearch : De Andrade_2016_Ann.Hum.Genet_80_203
PubMedID: 27346732

Title : Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population - Bono_2015_Neurochem.Int_81_57
Author(s) : Bono GF , Simao-Silva DP , Batistela MS , Josviak ND , Dias PF , Nascimento GA , de Souza RLR , Piovezan MR , Souza RK , Furtado-Alle L
Ref : Neurochem Int , 81 :57 , 2015
Abstract : 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.
ESTHER : Bono_2015_Neurochem.Int_81_57
PubMedSearch : Bono_2015_Neurochem.Int_81_57
PubMedID: 25624079

Title : Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE) activity and changes its relationship with lipids - Guimaraes_2014_Genet.Mol.Biol_37_1
Author(s) : Guimaraes LO , de Andrade FA , Bono GF , Setoguchi TE , Brandao MB , Chautard-Freire-Maia EA , Dos Santos IC , Picheth G , Faria AC , Rea RR , de Souza RLR , Furtado-Alle L
Ref : Genet Mol Biol , 37 :1 , 2014
Abstract : Many conditions interfere with butyrylcholinesterase (BChE) activity, e.g., pregnancy or presence of the BCHE gene variant -116A can decrease activity whereas obesity and types I and II diabetes mellitus can increase activity. In this study, we examined BChE activity, -116A and 1615A BCHE gene variants, and anthropometric and biochemical variables associated with diabetes in patients with gestational diabetes mellitus (GDM) and in healthy pregnant women. BChE activity was measured spectrophotometrically using propionylthiocholine as substrate and genotyping of the -116 and 1615 sites of the BCHE gene was done with a TaqMan SNP genotyping assay. Three groups were studied: 150 patients with GDM, 295 healthy pregnant women and 156 non-pregnant healthy women. Mean BChE activity was significantly lower in healthy pregnant women than in women from the general population and was further reduced in GDM patients. BChE activity was significantly reduced in carriers of -116A in GDM patients and healthy pregnant women. Although GDM patients had a significantly higher mean body mass index (BMI) and triglycerides than healthy pregnant women, they had lower mean BChE activity, suggesting that the lowering effect of GDM on BChE activity was stronger than the characteristic enhancing effect of increased BMI and triglycerides.
ESTHER : Guimaraes_2014_Genet.Mol.Biol_37_1
PubMedSearch : Guimaraes_2014_Genet.Mol.Biol_37_1
PubMedID: 24688284

Title : [Butyrylcholinesterase activity and cardiovascular risk factors in obese adolescents submitted to an exercise program] - Eisfeld Milano_2013_Arq.Bras.Endocrinol.Metabol_57_533
Author(s) : Eisfeld Milano Gerusa , Leite N , Chaves TJ , Eisfeld Milano Gisele , de Souza RLR , Furtado-Alle L
Ref : Arq Bras Endocrinol Metabol , 57 :533 , 2013
Abstract : OBJECTIVE: To evaluate the effect of 12 weeks of physical exercise (PE) on cardiovascular risk factors and BChE activity in obese adolescents. SUBJECTS AND
METHODS: The sample consisted of 24 obese adolescents and 51 normal weight controls. The following variables were measured in the initial stage and after 12 weeks: weight, height, BMI, waist circumference (WC), fat percentage (% F), maximal oxygen uptake (VO2max), systolic (SBP) and diastolic (DBP) blood pressure, glucose (GLY) and insulin (INS) at baseline and after 120 min, triacylglycerol (TG), total cholesterol (TC), LDL cholesterol, HDL cholesterol, and BChE activity (kU/l).
RESULTS: After the intervention, there was significant reduction in BMI, WC, %F, TG, GLI 120, INS 120 min, and BChE activity. CONCLUSION: The reduction in BChE activity, observed after physical exercise, was accompanied by the reduction of the variables associated with cardiovascular risk and obesity, indicating that BChE can be used as a secondary marker for the risk associated with early onset obesity.
ESTHER : Eisfeld Milano_2013_Arq.Bras.Endocrinol.Metabol_57_533
PubMedSearch : Eisfeld Milano_2013_Arq.Bras.Endocrinol.Metabol_57_533
PubMedID: 24232818

Title : -116A and K BCHE gene variants associated with obesity and hypertriglyceridemia in adolescents from Southern Brazil - Chaves_2013_Chem.Biol.Interact_203_341
Author(s) : Chaves TJ , Leite N , Milano GE , de Souza RLR , Chautard-Freire-Maia EA , Furtado-Alle L
Ref : Chemico-Biological Interactions , 203 :341 , 2013
Abstract : Butyrylcholinesterase (BChE) has been associated to body mass index (BMI), weight, cholesterol and triglyceride levels. -116A (rs1126680) and K (A539T, 1615A, rs1803274) BCHE gene variants had previously been associated to BChE activity, weight and BMI variance in adults. The present study examined -116A and K variants, BChE activity, anthropometric and biochemical variables associated with obesity in adolescents (120 obese and 150 non-obese from Curitiba, Brazil). Both -116A and K variants were found with significantly lower frequencies (p<0.05) in obese adolescents when compared with non-obese adolescents and with the general population. Mean BChE activity (KU/L) was significantly higher in obese adolescents when compared with non-obese adolescents and with the general population. Analyzing only the obese adolescents, it was found that carriers of the -116A variant showed lower BChE activity and higher triglyceride levels than homozygotes for the usual allele. Indeed, obese carriers of the -116A variant had triglyceride levels considered high according to reference values for serum triglycerides in Brazilian adolescents. These results show: (1) a protective effect of -116A and K variants on juvenile obesity risk, suggesting a role for the BCHE gene on juvenile onset obesity different from that observed on adult onset obesity and (2) an association of the -116A variant with hypertriglyceridemia in obese adolescents probably because of its effect on lowering BChE activity and consequently diminishing the enzyme capability of maintaining homeostasis on lipid metabolism during the metabolic stress caused by obesity.
ESTHER : Chaves_2013_Chem.Biol.Interact_203_341
PubMedSearch : Chaves_2013_Chem.Biol.Interact_203_341
PubMedID: 23000450

Title : Association analysis between K and -116A variants of butyrylcholinesterase and Alzheimer's disease in a Brazilian population - Simao-Silva_2013_Chem.Biol.Interact_203_358
Author(s) : Simao-Silva DP , Bertolucci PH , de Labio RW , Payao SL , Furtado-Alle L , de Souza RLR
Ref : Chemico-Biological Interactions , 203 :358 , 2013
Abstract : In Alzheimer's disease (AD) a reduction in acetylcholinesterase (AChE) and an increase in butyrylcholinesterase (BChE) activity are observed. K variant (539T) is the most common variant of the BCHE gene and, although controversial, several studies reported association between K variant and AD. Previous results showed that the K variant alone is not capable of diminishing BChE activity, depending on the presence of the -116A variant. Considering that, we conducted a case-control association study using a clinically well defined group of AD patients (n=82) and age and sex matched control subjects (EC; n=78) in order to test the association with these variations of BCHE gene in a Brazilian population. The allele, genotype and haplotype frequencies of the K and the -116A variants of BCHE gene were not significantly different between cases and controls. Although not reaching statistical significance, the results suggested that the presence of -116A variant may have a protective effect against AD. The association of the K variant with AD in a controversial manner in different surveys is probably caused by its linkage disequilibrium with -116A that, by reducing BChE activity, potentially increases cholinergic transmission in comparison with usual genotypes.
ESTHER : Simao-Silva_2013_Chem.Biol.Interact_203_358
PubMedSearch : Simao-Silva_2013_Chem.Biol.Interact_203_358
PubMedID: 23022600

Title : 1914G variant of BCHE gene associated with enzyme activity, obesity and triglyceride levels - Lima_2013_Gene_532_24
Author(s) : Lima JK , Leite N , Turek LV , de Souza RLR , da Silva Timossi L , Osiecki AC , Osiecki R , Furtado-Alle L
Ref : Gene , 532 :24 , 2013
Abstract : Polymorphisms of butyrylcholinesterase (BChE) have been reported to be associated to weight, BMI variance and hypertriglyceridemia in adults and adolescents. The aim of the present study was to investigate the association of -116A (SNP: G/A; rs1126680) and 1914G (SNP: A/G; rs3495) variants of BCHE gene with anthropometric and biochemical variables associated with obesity in population sample of 115 individuals, from Southern Brazil. Participants were grouped in two categories: obese (BMI>/=30) and non-obese (BMI<30). The 1914G allele showed significantly higher frequency in the obese group, and carriers of 1914G allele showed lower mean BChE activity when compared to 1914A carriers (p=0.006). Higher means of BMI (p=0.02) and triglyceride (TG; p=0.01) were found in 1914G carriers (BMI=27.57kg/m(2); TG=150.8mg/dL) when compared to 1914A homozygotes (BMI=25.55kg/m(2); TG=107.9mg/dL). Carriers of the -116A allele showed lower mean BChE activity than usual homozygotes, and the -116A variant was found in cis with 1914G (p<0.0001; D'=1). The region of BCHE gene that contains the 1914G mutation site is target of microRNAs (miRs) and the response of BChE to glucocorticoids is especially influenced by these miRs. Therefore, it is possible that the 1914G allele can be interfering in gluconeogenesis, hyperglycemia, lipolysis and body fat distribution. This lower activity may cause an imbalance in lipid metabolism, which may lead to an increased predisposition to obesity and to a lower ability to maintain metabolic homeostasis.
ESTHER : Lima_2013_Gene_532_24
PubMedSearch : Lima_2013_Gene_532_24
PubMedID: 24001779

Title : Copy number variation in ACHE\/EPHB4 (7q22) and in BCHE\/MME (3q26) genes in sporadic breast cancer - Boberg_2013_Chem.Biol.Interact_203_344
Author(s) : Boberg DR , Batistela MS , Pecharki M , Ribeiro EM , Cavalli IJ , Lima RS , Urban CA , Furtado-Alle L , de Souza RLR
Ref : Chemico-Biological Interactions , 203 :344 , 2013
Abstract : Gene amplifications and deletions are common changes in human cancer cells. Previous studies indicate that the regions, where the ACHE (7q22) and BCHE (3q26.1-q26.2) genes are localized, are suffering such structural modifications in breast cancer. Therefore, the products of these genes, acetylcholinesterase and butyrylcholinesterase, respectively, are related to the process of cell differentiation and proliferation, as well as apoptosis. This study also included two other genes involved in tumorigenesis, the EPHB4 (7q22.1) and MME (3q21-27). The aim of this study was to verify amplification and/or deletion in the ACHE, BCHE, EPHB4 and MME genes in 32 samples of sporadic breast cancer. The gene alterations were detected using real-time PCR and determined by relative quantification with the standard curve method. All samples presented genetic alterations, showing a higher tendency for amplification of the ACHE (62.5% vs. 37.5%; p>0.1) and EPHB4 (53.13% vs. 46.88%; p>0.5) genes, and for deletions of the BCHE and MME genes (56.25% vs. 43.75% for both; p>0.5). A positive correlation was found between alterations in ACHE-EPHB4 and BCHE-MME pairs (rs=0.5948; p=0.0004; rs=0.3581; p=0.0478, respectively) indicating that these changes comprise a wide region. In conclusion, the results suggest that these genomic regions may contain important genes for this pathology, such as the oncogenes MET (7q31) and PIK3CA (3q26), and thus being interesting targets for future studies in breast cancer research.
ESTHER : Boberg_2013_Chem.Biol.Interact_203_344
PubMedSearch : Boberg_2013_Chem.Biol.Interact_203_344
PubMedID: 23063927

Title : Investigation of Association between Susceptibility to Leprosy and SNPs inside and near the BCHE Gene of Butyrylcholinesterase - Gomes_2012_J.Trop.Med_2012_184819
Author(s) : Gomes HJ , de Souza RLR , Prevedello FC , Mira MT , Chautard-Freire-Maia EA
Ref : J Trop Med , 2012 :184819 , 2012
Abstract : Leprosy is a chronic disease caused by Mycobacterium leprae and affects the skin and the peripheral nervous system. Butyrylcholinesterase is coded by the BCHE gene, and the atypical allele (70G; rs1799807) has been investigated as a leprosy risk factor, with conflicting results. The present study estimated the frequencies of variants of rs1799807 and of five additional SNPs at the BCHE gene or near it: rs1126680, rs1803274, rs2863381, rs4440084, and rs4387996. A total of 167 patients and 150 healthy controls were genotyped by TaqMan PCR. Significantly higher allelic (70G) and genotypic (70DG) frequencies in rs1799807 were found in the patient group, with odds ratio (OR) of 6.33 (1.40 to 28.53) for the heterozygote. This finding was replicated in a comparison of the cases against a control group of 361 blood donors. The present data suggest that the atypical BChE variant may predispose to leprosy per se.
ESTHER : Gomes_2012_J.Trop.Med_2012_184819
PubMedSearch : Gomes_2012_J.Trop.Med_2012_184819
PubMedID: 22523498

Title : Effects of physical exercise on butyrylcholinesterase in obese adolescents - Silva_2012_Genet.Mol.Biol_35_741
Author(s) : Silva IM , Leite N , Boberg D , Chaves TJ , Eisfeld Milano Gisele , Bono GF , de Souza RLR , Furtado-Alle L
Ref : Genet Mol Biol , 35 :741 , 2012
Abstract : The aim of the present study was to evaluate the effect of a 12 week program of physical exercise (PE) on butyrylcholinesterase (BChE) in obese adolescents. This study compared obese adolescents (N = 54) before and after PE, regarding the relative intensity (RI) and activity of different molecular forms (G1, G2, G4 and G1-ALB) of BChE found in plasma. Waist circumference (WC) and lipid profile were also assessed before and after PE. It was shown that before PE, mean plasma BChE activity was significantly higher in obese than in non-obese adolescents and that it was significantly reduced after PE, becoming similar to that found in non-obese adolescents. Lipid profile and WC also changed in response to PE. These results are consistent with studies that found a correlation between BChE and lipid metabolism and suggest that PE may have led to a physiological regularization of plasma BChE activity. Although mean BChE activity of each isoform was significantly reduced by PE, their RI did not change. This is in accordance with a previous suggestion that this proportion is maintained under factors such as obesity, and may therefore be important for BChE functions.
ESTHER : Silva_2012_Genet.Mol.Biol_35_741
PubMedSearch : Silva_2012_Genet.Mol.Biol_35_741
PubMedID: 23271933

Title : Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes - Dantas_2011_Genet.Mol.Biol_34_205
Author(s) : Dantas VG , Furtado-Alle L , de Souza RLR , Chautard-Freire-Maia EA
Ref : Genet Mol Biol , 34 :205 , 2011
Abstract : Ghrelin coded by the GHRL gene is related to weight-gain, its deactivation possibly depending on its hydrolyzation by butyrylcholinesterase (BChE) encoded by the BCHE gene, an enzyme already associated with the body mass index (BMI). The aim was to search for relationships between SNPs of the GHRL and BCHE genes with BChE activity, BMI and obesity in 144 obese and 153 nonobese Euro-Brazilian male blood donors. In the obese individuals, a significant association with higher BChE activity, in the 72LM+72MM; -116GG genotype class (GHRL and BCHE genes, respectively) was noted. No significant differences were found otherwise, through comparisons between obese and control individuals, of genotype and allele frequencies in SNPs of the GHRL gene (Arg51Gln and Leu72Met), or mean BMI between 72LL and 72LM+72MM genotypes. Although there appears to be no direct relationship between the examined GHRL SNPs and BMI, the association of the 72M SNP with higher BChE activity in obese subjects probably points to a regulatory mechanism, thereby implying the influence of the GHRL gene on BChE expression, and a consequential metabolic role in the complex process of fat utilization.
ESTHER : Dantas_2011_Genet.Mol.Biol_34_205
PubMedSearch : Dantas_2011_Genet.Mol.Biol_34_205
PubMedID: 21734817

Title : Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer - Bernardi_2010_Cancer.Genet.Cytogenet_197_158
Author(s) : Bernardi CC , Ribeiro Ede S , Cavalli IJ , Chautard-Freire-Maia EA , de Souza RLR
Ref : Cancer Genet Cytogenet , 197 :158 , 2010
Abstract : Increasing evidence supports the involvement of acetylcholinesterase and butyrylcholinesterase in cell proliferation control and differentiation, reinforcing the hypothesis that these enzymes might have an influence in tumorigenesis. It has already been shown that the cholinesterase genes are structurally altered or aberrantly expressed in a variety of tumor types. In this study, amplifications and deletions in the ACHE and BCHE genes were investigated in sporadic breast tumors using real-time polymerase chain reaction and the relative quantification method. The majority of the tumor tissues showed a notable number of both deletions and amplifications: 65.7% and 22.9%, respectively, in BCHE and 45.7% and 31.4%, respectively, in ACHE. Deletion of the ACHE gene was significantly correlated with amplification of the protooncogene ERBB2. Tumor size was significantly higher when the ACHE gene was amplified, and the total number of alterations (amplifications plus deletions) of the BCHE gene was positively correlated with tumor malignancy grade.
ESTHER : Bernardi_2010_Cancer.Genet.Cytogenet_197_158
PubMedSearch : Bernardi_2010_Cancer.Genet.Cytogenet_197_158
PubMedID: 20193849

Title : Molecular forms of butyrylcholinesterase and obesity - Boberg_2010_Genet.Mol.Biol_33_452
Author(s) : Boberg DR , Furtado-Alle L , de Souza RLR , Chautard-Freire-Maia EA
Ref : Genet Mol Biol , 33 :452 , 2010
Abstract : This study compared obese (N = 134) and unobese (N = 92) male blood donors, regarding the relative intensity (RI) and activity of different molecular forms (G1, G2, G4 and G1-ALB) of butyrylcholinesterase (BChE, EC found in plasma, thereby searching for an association between these variables with obesity and SNPs of exons 1 and 4 of the BCHE gene. It was shown that obese and unobese individuals do not differ in the RI of each BChE band, even when classifying the sample into three genotypes of exons 1 and 4 of the BCHE gene (-116GG/539AA, -116GG/539AT, -116GA/539AT). Although the mean BChE activity of each band was significantly higher in obese than in unobese blood donors, the proportions of BChE bands were maintained, even under the metabolic stress associated to obesity, thereby leading to infer that this proportion is somehow regulated, and may therefore be important for BChE functions.
ESTHER : Boberg_2010_Genet.Mol.Biol_33_452
PubMedSearch : Boberg_2010_Genet.Mol.Biol_33_452
PubMedID: 21637414

Title : Two new mutations of the human BCHE gene (IVS3-14T>C and L574fsX576) - Parmo-Folloni_2008_Chem.Biol.Interact_175_135
Author(s) : Parmo-Folloni F , Nunes K , Lepienski LM , Mikami LR , de Souza RLR , Tsuneto LT , Petzl-Erler ML , Chautard-Freire-Maia EA
Ref : Chemico-Biological Interactions , 175 :135 , 2008
Abstract : The genetic variation of human butyrylcholinesterase is associated with the majority of prolonged cases of apnea in patients submitted to the muscle relaxant succinylcholine. The present study reports two new mutations of the BCHE gene in 346 Euro-Brazilians: IVS3-14T>C found in five heterozygotes (allele frequency: 0.72+/-0.32%) and L574fsX576 found in one heterozygote (allele frequency: 0.14+/-0.14%). These two variants were not found in 85 Guarani Amerindians. It is not expected that the IVS3-14T>C mutation may interfere in the splicing process and that the mutation found in exon 4 (L574fsX576) may disturb BChE tetramerization and activity.
ESTHER : Parmo-Folloni_2008_Chem.Biol.Interact_175_135
PubMedSearch : Parmo-Folloni_2008_Chem.Biol.Interact_175_135
PubMedID: 18555211

Title : Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian population - Mikami_2008_Pharmacogenet.Genomics_18_213
Author(s) : Mikami LR , Wieseler S , de Souza RLR , Schopfer LM , Nachon F , Lockridge O , Chautard-Freire-Maia EA
Ref : Pharmacogenet Genomics , 18 :213 , 2008
Abstract : Human butyrylcholinesterase (BChE; EC is codified by the BCHE gene (3q26.1-q26.2) in which 65 variants have been identified. BChE is a scavenger of organophosphorus and carbamate compounds and hydrolyzes succinylcholine, mivacurium and cocaine. The present study describes 12 naturally occurring BCHE mutations including five new mutations (K12R, G15G, V294M, G333C and R470W) identified in 366 blood donors from Southern Brazil. Exons 2 and 4 of the BCHE gene were examined by PCR-SSCA and samples with unexpected electrophoretic patterns were sequenced. The respective nucleotide substitution that characterizes each of the four new nonsynonymous mutations was introduced into BCHE cDNA by site directed mutagenesis and transfected into human embryonic kidney 293T cells and/or Chinese hamster ovary cells. The catalyzed hydrolysis of butyrylthiocholine (BTC) by BChE was measured by the Ellman method. Enzyme kinetic parameters obtained after the expression of the respective recombinant BChE evaluated the effects of the four nonsynonymous mutations. Thirty-four out of 366 individuals carried a BChE mutation in exon 2. The K variant mutation, A539T in exon 4, was present in one out of three persons. Gene expression showed that only one of the newly identified mutations (G333C) altered BChE activity, leading to a decrease of about 80% in relation to the wild-type enzyme.
ESTHER : Mikami_2008_Pharmacogenet.Genomics_18_213
PubMedSearch : Mikami_2008_Pharmacogenet.Genomics_18_213
PubMedID: 18300943

Title : Association of variants of the -116 site of the butyrylcholinesterase BCHE gene to enzyme activity and body mass index - Furtado-Alle_2008_Chem.Biol.Interact_175_115
Author(s) : Furtado-Alle L , Andrade FA , Nunes K , Mikami LR , de Souza RLR , Chautard-Freire-Maia EA
Ref : Chemico-Biological Interactions , 175 :115 , 2008
Abstract : Butyrylcholinesterase (BChE) is coded by the BCHE gene that presents four exons. The non-codifying exon 1 presents two variants -116G and -116A, being -116A preferentially in cis conformation with the 539T variant (K) of exon 4 which was associated with lower BChE activity and lower body mass index (BMI) variance. This study analyzed the frequency of -116 variants and the relation of genotypes -116GG;539AA, -116GG;539AT and -116GA;539AT with BChE activity and with BMI in Euro-Brazilian blood donors. The frequency of -116A was significantly higher (18.9%) in the low BChE activity group when compared to obese (8.6%) and normal BMI (9.3%) groups. In obese and non-obese groups, the -116GA;539AT genotype showed significantly lower mean BChE activity when compared to the -116GG;539AA genotype and in obese individuals the -116GA;539AT genotype also showed lower BChE activity than the -116GG;539AT genotype. In a sample selected independently of BMI, the -116GA;539AT genotype showed significantly higher BMI variance (21.75) when compared to -116GG;539AA (12.14) and to -116GG;539AT (13.43) genotypes, indicating that the association with higher BMI variance only occurs in the presence of the -116A variant. In the obese sample, the -116GG;539AT genotype presented mean (32.1+/-0.3) and variance (2.3) of BMI significantly lower than those found in the -116GG;539AA (33.0+/-0.3 and 9.9, respectively) and -116GA;539AT (33.7+/-0.7 and 12.2, respectively) genotypes. These data show that: (1) the K (539T) variant alone is not associated with decreased BChE activity, being the 5' UTR -116A variant necessary for this decrease, probably by affecting transcription and/or translation of the BCHE gene; (2) samples with different BMI distributions present different relationships between BCHE genotypes and BMI, reinforcing the hypothesis of a role for the BCHE gene in BMI determination.
ESTHER : Furtado-Alle_2008_Chem.Biol.Interact_175_115
PubMedSearch : Furtado-Alle_2008_Chem.Biol.Interact_175_115
PubMedID: 18550040

Title : Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase - Mikami_2007_Pharmacogenet.Genomics_17_681
Author(s) : Mikami LR , Wieseler S , de Souza RLR , Schopfer LM , Lockridge O , Chautard-Freire-Maia EA
Ref : Pharmacogenet Genomics , 17 :681 , 2007
Abstract : The present paper examined the effects of three non synonymous BCHE mutations (G75R, E90D and /99M) on enzyme kinetic parameters obtained after the expression of the respective recombinant BChEs. The respective nucleotide substitution that characterizes each of the three variants was introduced into BCHE cDNA by site directed mutagenesis and transfected into human embryonic kidney 293 T cells and Chinese hamster ovary cells (for E90D). BChE catalysed hydrolysis of butyrylthiocoline (BTC) was measured by Ellman method. The expression results showed that: (1) the activity of the G75R enzyme represents approximately 45% of the wild-type activity, whereas that of the I99M enzyme does not differ from the wild-type; (2) the E90D enzyme presents a silent phenotype; disruption of the salt bridge between E90 and R42 may cause the enzyme to be rapidly degraded inside the cells. In homozygous form the E90D enzyme may confer increased susceptibility to succinylcholine, but may delay cognitive impairment in aged individuals. BChE genotyping may become important for estimating prognosis, and the knowledge of the genetic variants of BChE in a particular population may be useful for carrying out the genotyping assays.
ESTHER : Mikami_2007_Pharmacogenet.Genomics_17_681
PubMedSearch : Mikami_2007_Pharmacogenet.Genomics_17_681
PubMedID: 17700357

Title : Variant K of butyrylcholinesterase and risk of early-onset type 1 diabetes mellitus in Euro-Brazilians -
Author(s) : Lepienski LM , de Souza RLR , Chautard-Freire-Maia EA , Alcantara VM , Rea RR
Ref : Diabetes Obes Metab , 8 :709 , 2006
PubMedID: 17026497

Title : Variant K of butyrylcholinesterase and types 1 and 2 of diabetes mellitus -
Author(s) : Lepienski LM , Alcantara VM , de Souza RLR , Rea RR , Chautard-Freire-Maia EA
Ref : Chemico-Biological Interactions , 157-158 :374 , 2005
PubMedID: 16429499

Title : Possible influence of BCHE locus of butyrylcholinesterase on stature and body mass index - de Souza_2005_Am.J.Phys.Anthropol_126_329
Author(s) : de Souza RLR , Fadel-Picheth C , Allebrandt KV , Furtado-Alle L , Chautard-Freire-Maia EA
Ref : Am J Phys Anthropol , 126 :329 , 2005
Abstract : Butyrylcholinesterase activity has been shown to be positively associated with weight and body mass index (BMI). The present study was carried out to search for an association between variants of the BCHE gene and weight, stature, and BMI on the basis of means and variances compared between nonusual variants and their respective usual controls. Individuals bearing the atypical mutation (N = 52) did not differ from their usual phenotype controls (N = 104) in these parameters. The BCHE*U/BCHE*K individuals (N = 222) presented a significantly higher BMI variance than their BCHE*U/BCHE*U controls (N = 222, F = 1.40, P = 0.012). This higher BMI variance does not seem to be an isolated effect of the K mutation, but appears to be the result of an interaction between the K allele and the usual allele, since no such difference in variance was detected between BCHE*K/BCHE*K individuals (N = 23) and their BCHE*U/BCHE*U (N = 23) controls. These data may suggest a relation between variability in the BCHE locus itself and BMI. Individuals with the BCHE UF phenotype (N = 45) showed a significantly higher mean stature (about 3 cm more; P = 0.02) than their controls with the usual phenotype (N = 135). A role in cell proliferation has been proposed for BCHE, and since growth depends on the number of mitoses, it is not unexpected that variants of this enzyme may influence body stature in different ways. This study reports the first data on the relation of BCHE alleles to anthropometric characters.
ESTHER : de Souza_2005_Am.J.Phys.Anthropol_126_329
PubMedSearch : de Souza_2005_Am.J.Phys.Anthropol_126_329
PubMedID: 15386241

Title : Four new mutations in the BCHE gene of human butyrylcholinesterase in a Brazilian blood donor sample - de Souza_2005_Mol.Genet.Metab_84_349
Author(s) : de Souza RLR , Mikami LR , Maegawa RO , Chautard-Freire-Maia EA
Ref : Mol Genet Metab , 84 :349 , 2005
Abstract : The genetic variation of human butyrylcholinesterase has been associated with height, body mass index, Alzheimer's disease, and response to xenobiotic agents. The present study reports four new mutations, found in the exon 2 of the BCHE gene, in a sample from 3001 Brazilian blood donors. The three nonsynonymous mutations and one synonymous mutation detected are: 223G-->C, G75R; 270A-->C, E90 D; 297T-->G, I99 M; 486T-->C, A162 A, respectively. All these variants are rare: 0.093+/-0.093% for the missense mutations and 0.137+/-0.137% for the synonymous mutation. A table with the 58 non-usual variants of butyrylcholinesterase is also presented.
ESTHER : de Souza_2005_Mol.Genet.Metab_84_349
PubMedSearch : de Souza_2005_Mol.Genet.Metab_84_349
PubMedID: 15781196

Title : Studies on a heterologous complex formed by human butyrylcholinesterase - de Souza_2003_Biochem.Genet_41_141
Author(s) : de Souza RLR , Furtado-Alle L , Diniz AC , Silva AC , Kaiss J , Petzl-Erler ML , Chautard-Freire-Maia EA
Ref : Biochemical Genetics , 41 :141 , 2003
Abstract : An electrophoretic band with butyrylcholinesterase activity was detected in 71 CHE2 C5+ and 378 CHE2 C5- individuals and was named C4/5 in view of its similar mobility to either C4 or C5, depending on the pH of the agar gel used. The present data suggest that C4/5 is a heterologous complex of butyrylcholinesterase. Although the C4/5 band may have the same mobility as C5, depending on the conditions of electrophoresis, our hypothesis is that these two bands result from the association of BChE with different molecules.
ESTHER : de Souza_2003_Biochem.Genet_41_141
PubMedSearch : de Souza_2003_Biochem.Genet_41_141
PubMedID: 12834044

Title : Variability of the paraoxonase gene (PON1) in Euro- and Afro-Brazilians - Allebrandt_2002_Toxicol.Appl.Pharmacol_180_151
Author(s) : Allebrandt KV , de Souza RLR , Chautard-Freire-Maia EA
Ref : Toxicol Appl Pharmacol , 180 :151 , 2002
Abstract : The human high-density lipoprotein-associated paraoxonase (EC; PON1) plays a role in the hydrolysis of organophosphorus compounds and against the oxidative damage of low-density lipoprotein. In the present study, variants of PON1 (55 and 192) were investigated by PCR-RFLP and PCR-SSCA in Euro- (N = 101) and Afro-Brazilians (N = 70). The PON1*55 and PON1*192 allele frequencies were significantly different in these ethnic groups (p < 0.05 and p < 0.001, respectively). The genotype frequencies for PON1*55 (LL, LM, and MM) in Euro- and Afro-Brazilians were 33, 56, and 11% and 47, 49, and 4%, respectively. The genotype frequencies for PON1*192 were significantly different in Euro- and Afro-Brazilians (QQ, QR, RR: 48, 42, and 10% and 21, 52, and 27%, respectively; p < 0.001). The haplotype frequency distributions were also significantly different in Euro- (LQ = 30.20%; LR = 30.69%; and MQ = 39.11%) and Afro-Brazilians (LQ = 24.97%; LR = 46.46%; MQ = 22.18%; and MR = 6.39%; p < 0.001). Linkage disequilibrium (D) in relation to the maximum expected value was higher in Euro- (100%) than in Afro-Brazilians (58%). We suggest that the high linkage disequilibrium in Caucasians and Asians characterized by the absence or very low frequency of the MR haplotype is mainly due to genetic drift and possibly also to natural selection favoring the PON1*192Q allele or a variant in linkage disequilibrium with it. This seems to be the first study on the PON1 variability at the DNA level in South American samples and one of the few studies on individuals of mixed African origin.
ESTHER : Allebrandt_2002_Toxicol.Appl.Pharmacol_180_151
PubMedSearch : Allebrandt_2002_Toxicol.Appl.Pharmacol_180_151
PubMedID: 12009854

Title : Frequencies of the butyrylcholinesterase K mutation in Brazilian populations of European and African origin - Souza_1998_Hum.Biol_70_965
Author(s) : de Souza RLR , Castro RM , Pereira L , Freund AA , Culpi L , Chautard-Freire-Maia EA
Ref : Hum Biol , 70 :965 , 1998
Abstract : The frequency of the butyrylcholinesterase K mutation was calculated on the basis of data obtained by polymerase chain reaction primer-introduced restriction analysis (PCR-PIRA). The population sample was composed of 177 Brazilians: 95 whites of predominantly European ancestry and 82 admixed individuals (European and African origin). The frequencies--18.4 +/- 2.8% for whites and 17.1 +/- 2.9% for admixed--did not differ from those previously obtained in North America, Scotland, Japan, and Denmark. The occurrence of the K mutation in Europeans, East Asians, and Africans suggests a relatively old origin for this mutation, and the similar frequencies found in these populations may suggest the operation of selective forces
ESTHER : Souza_1998_Hum.Biol_70_965
PubMedSearch : Souza_1998_Hum.Biol_70_965
PubMedID: 9780523

Title : Studies on a Molecular Form (C4\/5) of Human Butyrylcholinesterase (BChE) -
Author(s) : de Souza RLR , Diniz AC , Silva AC , Kaiss J , Chautard-Freire-Maia EA
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :598 , 1998

Title : Frequency of the F2 Mutation of Human Butyrylcholinesterase in a Random Population Sample from Southern Brazil -
Author(s) : de Souza RLR , Maegawa GH , Furtado L , Akel C , Castro RM , Chautard-Freire-Maia EA
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :600 , 1998

Title : Frequencies of the Butyrylcholinesterase K Mutation in Southern Brazilian Population Samples of European and African Origin -
Author(s) : de Souza RLR , Castro RM , Pereira L , Freund AA , Culpi L , Chautard-Freire-Maia EA
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :601 , 1998