CHE2 C5 Research Articles

Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study.

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. 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. 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. 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.

Association between RAPH1 Gene Haplotypes and CHE2 Locus Phenotypes

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.

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

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.

Butyrylcholinesterase and diabetes mellitus in the CHE2 C5- and CHE2 C5+ phenotypes

To investigate the relationship between butyrylcholinesterase (BChE) activities (total and band specific) and diabetes mellitus. BChE activities (BChEA, AC(4/5), AC(OF) and RC(5)) were analyzed in 101 type 1 (DM1) and in 145 type 2 (DM2) diabetic patients, in relation to phenotype, weight and incidence of metabolic syndrome (MS) in these patients. The C(4/5) and C(5) complex were separated from other molecular forms (C(OF)) using an acid agar gel. The BChE activity (BChEA) and the absolute activities of C(4/5) (AC(4/5)) and C(OF) (AC(OF)) showed a high positive correlation coefficient to weight in the CHE2 C5- group, while the relative activity of C5 complex (RC5) showed a negative correlation to weight. The present study suggests that the positive correlation of the BChE activities to diabetes mellitus and to insulin resistance may depend on the CHE2 locus variability. High values of BChE activities were associated with insulin resistance only in CHE2 C5- diabetic patients, while in CHE2 C5+ diabetic patients, the presence of C(5) complex, especially in a relatively high proportion, leads to less fat storage and better protection against metabolic syndrome.

Butyrylcholinesterase genetic variability in Guarani Amerindians from the Brazilian state of Mato Grosso do Sul

Human butyrylcholinesterase (BChE; EC 3.1.1.8) is a polymorphic enzyme coded by the BCHE gene (3q26.1-q26.2) while the CHE2 gene (2q33-q35) determines a still not characterized substance that forms a complex with BChE (C5), being the CHE2 C5+ and CHE2 C5- phenotypes detected in electrophoresis. The present study investigated BCHE and CHE2 variability and the BChE activity of Brazilian Guarani Amerindians from the Kaiowa and Nandeva sub-groups living in several indigenous territories in the Brazilian state of Mato Grosso do Sul. The frequency of the BCHE exon 2 D70G (A) allele was 0.60% ± 0.35% while that of the BCHE exon 2 G390V (F-2) allele, never before screened in Amerindians, was 8.82% ± 1.35%. This is the first time that the BCHE gene exon 4 A539T (K) allele has been surveyed in Brazilian Amerindians where it was found at a frequency of 3.69% ± 0.85%, similar to that found in Chilean Mapuche Amerindians. The BCHE gene variability seen in this survey differs from that of non-isolated populations in respect to both A539T and G390V allele frequency. The CHE2 C5+ phenotype frequency was 14.40% ± 2.22% and falls within the range of that found for other Brazilian Amerindian samples.

Butyrylcholinesterase activity and metabolic syndrome in obese patients

Total butyrylcholinesterase activity (EC 3.1.1.8) was previously suggested as a marker for metabolic syndrome. The present study examined total butyrylcholinesterase activity and the relative and absolute activities of two butyrylcholinesterase electrophoretic bands (C(4/5) and C(OF) in 99 obese individuals (body mass index > or = 30 kg/m2) presenting the CHE2 C5- phenotype of the CHE2 gene. Anthropometric, hormonal and biochemical variables already associated with metabolic syndrome were also examined. The data from these obese individuals of the CHE2 C5- phenotype show that total butyrylcholinesterase activity and the absolute activities of the C(4/5) and C(OF) electrophoretic bands are associated with metabolic syndrome and with variables related to it. These butyrylcholinesterase activities do not behave as independent risk factors for metabolic syndrome, but can be considered as secondary markers for this syndrome in obese individuals with the CHE2 C5- phenotype.

Butyrylcholinesterase and obesity in individuals with the CHE2 C5+ and CHE2 C5- phenotypes.

To investigate the association between butyrylcholinesterase (BChE) activities (total and band specific) and body mass index (BMI) in obese and nonobese individuals, considering other variables (anthropometric, biochemical and hormonal) and the leanness process. Obese (BMI> or =30 kg/m(2); N=181) and nonobese individuals (N=265), classified according to the CHE2 locus phenotypes, with the obese patients being followed-up when submitted to a weight-loss program. Anthropometric (weight, height, BMI, waist, waist/hip ratio-WHR, triceps and subscapular skinfolds, percentage of body fat and arterial pressures), hormonal (insulin, estradiol-E(2), triiodothyronine-T(3) and thyroxine-T(4)) and biochemical (glucose, total cholesterol, HDL-C, triglycerides, uric acid, urea, creatinine, sodium, potassium and BChE activities) variables. Although obese CHE2 C5- individuals presented higher mean BChE activities than their CHE2 C5- controls and diminished mean activities with leanness, similar comparisons did not show any difference in the CHE2 C5+ group. Furthermore, the mean serum potassium values of obese individuals were significantly higher in the CHE2 C5+ than in the CHE2 C5- phenotype. The BChE activities were less related to BMI in obese CHE2 C5- individuals than in their controls. In the CHE2 C5- obese group, significant regression coefficients were found between BChE activity variables and BMI (+), ethnic origin (higher in Euro-Brazilians), sex (higher in males), diastolic pressure (-), triceps skinfold (+), total cholesterol (+), T(3) (+) and E(2) (-). The main findings in the CHE2 C5+ obese group: mean insulin levels decreased with leanness and a significant correlation was detected between the C(5) complex activity and creatinine (+), insulin (-) and WHR (-); a significantly higher frequency of weight loss occurred compared to the CHE2 C5- group. In the present study, different relations between obesity and some of the studied variables were found when CHE2 C5+ and CHE2 C5- individuals were compared.

The variable expression of the C4/5 complex of human butyrylcholinesterase and body mass index.

The activity of a supposedly heteromeric complex (C4/5) of butyrylcholinesterase (BChE; EC 3.1.1.8) was analyzed in relation to body mass index (BMI). The activities of the C4/5 and C(OF) (other molecular forms) bands in CHE2 C5- (n = 447) and CHE2 C5+ (n = 88) individuals were quantified by densitometry. Since the absolute activity of C4/5 (AC4/5) showed the highest correlation coefficient with weight in the CHE2 C5- phenotype when compared to the other BChE activity variables (total, relative C4/5, and absolute C(OF)), this variable was used for the classification of 51 CHE2 C5-individuals into three groups (low, average, and high), paired by sex, age, and ethnic origin. The low AC4/5 group was found to present a significantly (p < 0.0001) lower mean BMI (22.9) than the other groups (average = 25.2, and high = 26.3). In the CHE2 C5+ individuals no statistically significant standardized regression coefficient was verified between BMI (dependent variable) and the C4/5, band activities. These data show that the behavior of the C4/5 band in relation to BMI differs between the CHE2 C5- and CHE2 C5+ phenotypes. While the C5 band of the CHE2 C5+ individuals is negatively associated with fat storage in the adipose cells, the present data show that the C4/5 band is positively associated with this storage in the CHE2 C5- phenotype.

Studies on a heterologous complex formed by human butyrylcholinesterase.

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.

Association of the CHE2 locus with body mass index and butyrylcholinesterase activity.

The butyrylcholinesterase (BChE; EC 3.1.1.8) activities of two electrophoretic bands of the CHE2 C5+ phenotype--C5 and C(OF) (other forms)--were quantified by densitometry in 100 individuals. The activity data suggested that, in addition to determining C5, the CHE2*C5+ allele also increases the level of other BChE forms. Since the relative activity of C5 showed the highest correlation coefficient with weight when compared with the other BChE activity variables (total, absolute C5, and absolute C(OF)), its median activity level was used for the classification of CHE2 C5+ phenotypes (faint and intense). Mean body mass index (BMI) was compared among the CHE2 locus phenotypes-controlled by sex, age, and ethnic group. It was shown that the intense CHE2 C5+ phenotype presents a significantly lower (p < 0.001) mean BMI (23.2) than the other phenotypes (faint CHE2 C5+ = 25.2; CHE2 C5- = 25.4). It seems that the relative COF activity is positively associated with fat storage, since CHE2 C5- and faint CHE2 C5+ phenotypes showed higher mean BMI than the intense CHE2 C5+ phenotype. Our hypothesis is that the presence of C5 in a relatively high proportion leads to less fat storage.

Butyrylcholinesterase Variants (BCHE and CHE2 Loci) Associated with Erythrocyte Acetylcholinesterase Inhibition in Farmers Exposed to Pesticides

Farmers exposed to pesticides and classified as mildly poisoned and controls on the basis of erythrocyte acetylcholinesterase (AChE) activity were examined for butyrylcholinesterase (BChE) genetic variability. The mildly poisoned group showed a significantly higher frequency of non-usual phenotypes (13.1%) than the control group (1.7%). These phenotypes showed a relative risk (RR) of 8.8 of erythrocyte AChE inhibition when compared to the usual phenotype. Among the subjects with the usual phenotype, the CHF2 C5- phenotype was more frequent in the mildly poisoned group (94.3%) than in the control group (81.0%), leading to an RR of 3.9 when compared to the CHE2 C5+ phenotype. When the total sample was classified into two groups (usual CHE2 C5+ and other phenotypes), the usual CHE2 C5+ phenotype was found to be responsible for a preventive fraction of about 14% of the cases of mild poisoning. The present data suggest that BChE genetic variability offers differential protection against erythrocyte AChE inhibition.

The C&lt;sub&gt;5&lt;/sub&gt; Isozyme of Serum Cholinesterase and Adult Weight

The relationship between the CHE2 locus of serum cholinesterase (BChE) and adult human weight was studied in a sample of 225 CHE2 C5+ individuals and 225 CHE2 C5- controls matched for sex, height, age and race. With respect to the intensity of the C5 band staining (scored 1-6), 113 individuals had faint C5 bands (scores 1-3) and 112 intense C5 bands (scores 4-6). The individuals with intense CHE2 C5+ phenotype showed a significantly lower mean adult weight (64.66 +/- 0.73 kg) when compared to their controls (70.59 +/- 0.97 kg) and a significant reduction in weight variance (59.81 and 105.18, respectively). Individuals with faint C5 bands, although showing a negative correlation between weight and C5 band intensity, did not differ from their controls in mean weight.