Vânia M. Alcântara

Butyrylcholinesterase activity and metabolic syndrome in obese patients.

Abstract 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 ≥30kg/m 2) 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.

Hormone replacement therapy in postmenopausal women and its effects on plasma lipid levels

Abstract Postmenopausal women run the same risks of coronary heart disease as men. The lipid alterations observed at this time reflect increased blood levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a), and reduced high-density lipoprotein cholesterol (HDL-C) levels. These changes lead to a higher risk of coronary artery disease, and hormonal therapy has a favorable effect on lipid metabolism. In this paper we review the literature on hormone replacement therapy (HRT) in postmenopausal women with the emphasis on the role of lipids in the pathogenesis of coronary heart disease, and on the action of estrogens and their correlation with progestogens, as well as routes of HRT administration. We conclude that the HRT changes the lipid profile in a potentially anti-atherogenic direction, usually reducing LDL-C and increasing HDL-C and triglycerides. Otherwise, for postmenopausal women with established coronary disease HRT is not recommended.

Frequency of the CHE1*K allele of serum cholinesterase in a sample from southern Brazil

The frequency of the CHE1*K allele was estimated as 2.04 +/- 2.02% in a population sample from Southern Brazil. Previously reported estimates refer to the British population and are significantly higher than the present one. Our hypothesis is that the British frequencies may represent overestimates due to ascertainment conditions.

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

OBJECTIVE To investigate the relationship between butyrylcholinesterase (BChE) activities (total and band specific) and diabetes mellitus. SUBJECTS AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Variant K of butyrylcholinesterase and risk of early-onset type 1 diabetes mellitus in Euro-Brazilians

Butyrylcholinesterase (BChE) is coded by the BCHE gene (3q26.1-3q26.2) and found in plasma, pancreas and several other parts of the body. Association of the K variant (1615nt: GCA!ACA; Ala539Thr) of this gene with type 2 diabetes mellitus was reported in one study [1] and not confirmed by another [2]. Considering that the K variant is associated with 30% reduction in BChE activity [3] and that low BChE activity was related to immune dysfunction [4], the hypothesis that this variant may be positively associated with type 1 diabetes mellitus (DM1) was tested. The patient sample included only Euro-Brazilians (n 1⁄4 72) recruited at the University Hospital of the Federal University of Paraná from 20 July 2001 to 5 March 2003. Only patients with a clear diagnosis of DM1 at disease onset were included, with plasma glucose levels exceeding 200 mg/dl on more than one occasion, overt symptoms and signs of the disease and immediate insulin requirement. Considering that tests for ICA, GAD and insulin antibodies were not available, patients with disease onset later than 35 years of age were not included. A control sample (886 EuroBrazilian blood donors; 16.0% females; mean age of 30.8 0.3 years) was used for allele and genotype frequency comparisons. Informed consent was obtained from the patients, and this research was ethically approved (CEP-HC; n 327.037/2001-04). Blood was collected with EDTA after at least 12 h fasting. BCHE genotypes were determined by PCRRFLP and by PCR-SSCA. BChE activity [5], levels of total cholesterol and triglycerides (enzymatic colorimetric – Merck SMT, Darmstadt, Germany), glucose (glucose hexokinase – Merck Mega, Darmstadt, Germany) and insulin (immunoassay – Abbott Diagnostics, IL, USA) were measured. The statistical analysis used STATISTICA FOR WINDOWS (STATSOFT, Tulsa, OK, USA) for variance and multiple regression analyses, RxC program for comparing groups on allele and genotype frequencies by Fisher exact test [6] and odds ratio for evaluating association. Variance analysis showed [table 1 (I)] that the usual genotype significantly differ from the UK þ KK genotype group owing to the means of age of disease onset (ADO) and of BChE activity. The lower BChE activity mean of the UK þ KK group when compared to the usual homozygote group was already expected [3]. By classifying the 72 patients according to the median of ADO (12 years), the frequency of the K allele in the patients with ADO 12 years was significantly higher than that in those with ADO >12 years and was also higher than that in the blood donor sample [table 1 (II)]. The genotype frequency distributions significantly differ in the same types of comparisons (B C and B D). Only age and BCHE genotype showed significance (b 1⁄4 0.46 0.10, t 1⁄4 4.46, p 1⁄4 3.5 10 , and b1⁄4 0.29 0.11, t 1⁄4 2.71, p 1⁄4 0.009, respectively) in a step-wise multiple regression analysis which considered ADO as dependent variable and 10 independent variables: BCHE genotype (UU 1⁄4 1 and UK þ KK 1⁄4 2), BChE activity, sex, age, BMI, WHR, glucose, total cholesterol, triglycerides and insulin]. When the distributions of individuals with and without the K variant were compared in the patient group with ADO 12 years and in the blood donor sample, the risk of DM1 was 2.1 higher for individuals with the K variant than for the usual homozygous genotype (odds ratio 1⁄4 2.1; 1.1–4.0 with 95% CI). When the total DM1 patient sample was compared to the control sample [table 1 (II)], no significant difference was found in allele or genotype frequencies. This fact may be interpreted in two different ways: (1) the K allele does not raise the risk for DM1, only predisposing for an earlier manifestation of this disease; (2) DM1 is of heterogeneous aetiology, and the K allele is positively associated only with the type 1 diabetes with earlier onset (immune-mediated), leading to a higher risk of this type of DM1. The present data suggest that the K variant or another variant in linkage disequilibrium with it may predispose to DM1 of earlier onset. The facts that BChE is a biological scavenger for organophosphorus compounds [7] that may provoke immune dysfunction [8] and that low BChE activity may be related to immune dysfunction [4] may be the rationale for the association found between the K variant and DM1 of relatively earlier onset.

Mucoproteína versus alfa-1-glicoproteína ácida: o que quantificar?

A quantificacao serica da alfa-1-glicoproteina (GPA) acida e util no diagnostico e no acompanhamento dos processos agudos resultantes de multiplas causas. Esta proteina tambem pode ser estimada pela quantificacao da mucoproteina (Muco), ensaio que reflete as glicoproteinas com elevado teor de acucar, entre as quais a GPA e majoritaria. O objetivo deste trabalho e verificar a correlacao e a performance analitica das determinacoes de mucoproteina (Muco) e alfa-1-glicoproteina acida (GPA), propondo uma equacao de regressao linear. Amostras de soros de 540 pacientes, com idades entre 10 e 79 anos (media de 34,6), predominando mulheres (71,3%), foram analisadas simultaneamente para Muco (Winzler, manual com reagentes proprios) e GPA (imunoturbidimetria automatizada, Roche; Cobas mira). A analise de regressao, fixando a Muco como variavel dependente, apresentou Muco (mg/dl em tirosina) = 0,031 x GPA (mg/dl) + 0,8 (r = 0,91); e, fixando o intercepto em zero, Muco = 0,039 x GPA (r = 0,98). A imprecisao interensaio foi de 23,4% e 5,2% (coeficiente de variacao), respectivamente, para Muco e GPA. Conclusao: a elevada variabilidade analitica da quantificacao da mucoproteina pelo metodo de Winzler recomenda que este ensaio seja substituido pela dosagem da alfa-1-glicoproteina acida. Quando necessario, recomendamos estimar a mucoproteina, quantificando a alfa-1-glicoproteina acida com ensaios de mesmo desempenho que o do utilizado neste trabalho, e usar a equacao de regressao AGP (mg/dl) x 0,039 = Muco (mg/dl em tirosina).

CHE1 UF Serum Cholinesterase Phenotype in Whites and Non-Whites from Southern Brazil as Determined by a New Method

A sample of 251 Whites and 818 Non-Whites, from Curitiba (southern Brazil), was typed with a new method with the aim of estimating the frequency of the CHE1*F allele. The frequency of this allele did not differ between Whites (0.60 +/- 0.34%) and Non-Whites (0.49 +/- 0.17%), being estimated as 0.51 +/- 0.15% for the whole sample. The use of the inhibitors DL-propranolol and RO2-0683 with alpha-naphthylacetate as substrate (at 37 degrees C) was efficient for discriminating between the CHE1 U and CHE1 UF phenotypes.

The Relation of Nutrition Index (NI) with the C4/5 Molecular Form of Butyrylcholinesterase (BChE) in Human Adults

Although the physiological role of BChE remains unknown there are several data suggesting its participation in lipid metabolism. In human plasma, BChE is present in at least 12 homo and heterologous molecular forms (1). One heterologous oligomer (C5) has been shown to have its activity negatively correlated to human adult weight (2). In the present study the relation between NI (weight/height2) and a supposedly hybrid BChE form, temporarily named C4/5 (3), was investigated.