Variabilidade da butirilcolinesterase em índios Guarani do Mato Grosso do Sul

Orientadora: Profa. Dra. Eleidi A. Chautard Freire MaiaDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Curso de Pós-Graduação em GenéticaInclui referências: p. 112-123Resumo: Nesse estudo foi analisada a variabilidade dos locos BCHE e CHE2 e a atividade da butirilcolinesterase (BChE; EC 3.1.1.8 ) em indígenas Guarani Kaiowá e Nandewa do Mato Grosso do Sul. A variabilidade do loco BCHE foi analisada através de fenotipagem por inibição enzimática e de PCR-SSCA. Foram analisados, por PCR-SSCA, dois fragmentos do exon 2, exons 3 e 4 do gene BCHE. A fenotipagem por inibição enzimática apresentou uma falha de cerca de 80% na detecção do alelo BCHE*390V (BCHE*F2; exon 2) responsável por um dos fenótipos resistente ao fluoreto. As frequências desse alelo foram de 1,55% ± 0,54% e de 6,98% ± 1 ,1 2 % (X2 = 18,6; p < 0,1 %), obtidas respectivamente por fenotipagem e por PCR-SSCA. Esses dados demonstram que, no caso da detecção da mutação BCHE*390V, a análise direta de ADN é preferível à fenotipagem por inibição enzimática. A mutação BCHE*70G (BCHE*A; exon 2), foi encontrada com frequência de 0,58% ± 0,30%. A análise do exon 3 não indicou a presença de nenhuma mutação. No exon 4 foi identificada, pela primeira vez em população ameríndia, a mutação BCHE*539T (BCHE*K) com frequência de 3,80% ± 0,80%. As atividades médias do grupo heterozigoto para mutação A e do grupo homozigoto para a mutação K são significativamente menores que a dos usuais. A análise do loco CHE2 indicou a presença do fenótipo CHE2 C5+ com frequência de 14,34% ± 2,18%, dentro do intervalo descrito na literatura para populações indígenas brasileiras. Não foi encontrada diferença significativa entre as médias de atividade enzimática dos indivíduos CHE2 C5+ (4,40 KU/L) e CHE2 C5- (4,27 KU/L). A atividade média da BChE dessa amostra Guarani (4,19% ± 1,39%) é significativamente menor que a média encontrada em Curitiba (4,89% ± 1,87%)

Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes

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

Molecular forms of butyrylcholinesterase and obesity

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 3.1.1.8) 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

Polymorphisms of APOE and APOB genes and dyslipidemias in a South Brazilian Cohort

Dyslipidemias are closely associated to the development of cardiovascular and cerebrovascular diseases, and therefore of great importance in public health. Many genes influence lipid levels, such as APOE and APOB. The present study aimed to investigate the effects of APOE gene alleles (rs7412: C&gt;T and rs429358: T&gt;C), and R3500Q mutation of APOB gene (rs5742904: G&gt;A) in lipid levels in a South Brazilian cohort. 214 individuals were analyzed and the frequencies of APOE ε2, ε3 and ε4 alleles were found respectively as 9.25 ± 0.4625; 70.5 ± 3.525&nbsp; and 20.25%± 1.401, while the frequency of R3500Q mutation of the APOB gene was 4.46 ± 1.00%. The ε4 allele was significantly more frequent in subjects with higher TC (Total Cholesterol) and LDL-C levels, while significantly higher frequency of the ε2 allele was found in individuals with higher HDL-C levels. The R3500Q mutation was suggested as a risk factor for higher TC levels, regardless gender and age (β = 21.326 ± 10377.78, p = 0.001).Las dislipidemias están asociadas con el desarrollo de enfermedades cardiovasculares y cerebrovasculares y, por tanto, son de gran importancia en la salud pública. Muchos genes influyen en los niveles de lípidos, como APOE y APOB. El presente estudio tuvo como objetivo investigar los efectos de los alelos del gen APOE (rs7412: C&gt;T y rs429358: T&gt;C) y la mutación R3500Q del gen APOB (rs5742904: G&gt;A) sobre los niveles de lípidos en una cohorte del sur de Brasil. Se analizaron 214 individuos y se encontró que las frecuencias de los alelos APOE ε2, ε3 y ε4 eran respectivamente 9,25 ± 0,4625; 70,5 ± 3,525 y 20,25% ± 1,401, mientras que la frecuencia de la mutación R3500Q del gen APOB fue de 4,46 ± 1,00%. El alelo ε4 fue significativamente más frecuente en individuos con niveles más altos de TC (colesterol total) y LDL-C, mientras que se encontró una frecuencia significativamente mayor del alelo ε2 en individuos con niveles más altos de HDL-C. La mutación R3500Q se sugirió como factor de riesgo para niveles más altos de CT, independientemente del sexo y la edad (β = 21,326 ± 10.377,78, p = 0,001).Dyslipidemias are closely associated to the development of cardiovascular and cerebrovascular diseases, and therefore of great importance in public health. Many genes influence lipid levels, such as APOE and APOB. The present study aimed to investigate the effects of APOE gene alleles (rs7412: C&gt;T and rs429358: T&gt;C), and R3500Q mutation of APOB gene (rs5742904: G&gt;A) in lipid levels in a South Brazilian cohort. 214 individuals were analyzed and the frequencies of APOE ε2, ε3 and ε4 alleles were found respectively as 9.25 ± 0.4625; 70.5 ± 3.525  and 20.25%± 1.401, while the frequency of R3500Q mutation of the APOB gene was 4.46 ± 1.00%. The ε4 allele was significantly more frequent in subjects with higher TC (Total Cholesterol) and LDL-C levels, while significantly higher frequency of the ε2 allele was found in individuals with higher HDL-C levels. The R3500Q mutation was suggested as a risk factor for higher TC levels, regardless gender and age (β = 21.326 ± 10377.78, p = 0.001)

Modulation of gene expression in mice treated with sugar and whey protein isolate / Modulação da expressão gênica em camundongos tratados com açúcar e isolado de proteína de soro de leite

This study compared the effects of three different types of diets (regular diet, high in sugar diet and high in sugar plus whey protein isolate supplementation diet) in mice. After 3 months, gene expression in liver and in adipose tissue was measured. We found that diets influenced in gene expression, but not supplementation. However, supplementation showed an anorectic effect, and protected animals from hepatic steatosis. In addition, the diets did not influence the myeloperoxidase activity in the adipose tissue, showing little influence on the infiltration of white cells in this tissue

Effects of physical exercise on butyrylcholinesterase in obese adolescents

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. Key words: BChE activity; physical exercise, obesity. Butyrylcholinesterase (BChE; EC 3.1.1.8) is coded by BCHE gene (3q26.1-q26.2), synthesized in the liver and distributed to several parts of the organism. Plasmatic BChE is found in four possible homomeric forms (G1 monomers, G2 dimmers, G3 trimers and G4 tetramers) or heteromeric forms formed in association with other proteins, such as albumin, G1-Alb (Masson, 1989). Several studies verified that BChE has a role in lipid metabolism The aim of this study was to compare the relative intensity (RI) of BChE isoforms revealed as bands (G1, G1-Alb, G2 and G4) in obese adolescents before and after 12 weeks of physical exercise (PE), and to search for a correlation between RI of BChE isoform bands, plasma BChE activity and PE. The sample comprised 54 obese adolescents (BMI above percentile 95 and mean age 12.6 ± 2.01), these being participants of a 12 week program of physical exercise. Aerobic exercise consisted of 50 to 100 min activity during the first four weeks. Intensity was set at 35%-55% of VO 2 peak, and was increased to 55%-75% during the next eight weeks. Plasma was sampled at baseline and after terminating the program. A sample of non-obese adolescents (N = 45; mean age 13.3 ± 2.15) was used to measure plasma BChE activity. The detection and analysis of BChE bands in plasma was made according to Mean plasma BChE activity was significantly reduced after the 12 weeks program (before: 7.66 ± 2.64 KU/L, after: 5.89 ± 2.34 KU/L; t = 2.96, p = 0.008). Accompanying BChE activity, waist circumference (WC; before: 97.41 ± 11.20 cm, after: 94.62 ± 10.51 cm, t = 3.6 and p = 0.03), LDL-cholesterol (LDL-C; before: 94.45 ± 20.83 mg/dL, after: 86.00 ± 16.37 mg/dL, t = 2.77 and p = 0.012) and triglycerides (TG; before: 114.30 ± 57.14 mg/dL, after: 82.75 ± 42.66 mg/dL, t = 3.1 and p = 0.006) also showed significant reduction with PE

A relationship between Single Nucleotide Polymorphism (SNP) in HSD11β1 and ADIPOQ genes and obesity related features in children and adolescents submitted on physical exercises

Obesity have overloaded the public health system and it is considered a multifactorial trait. This study aimed to verify if Single Nucleotide Polymorphisms (SNP) in ADIPOQ (rs1501299) and HSD11β1 (rs12086634) genes influence the anthropometric and biochemical outcomes (Body Mass Index (BMI), Abdominal Circumference (AC), Low Density Lipoprotein (LDL-C), High Density Lipoprotein (HDL-C), Triglycerides (TG), Total Cholesterol (TC) and Glucose (Glu)) before and after practicing physical exercises training modalities, in a sample of 126 Southern Brazilian children and adolescents. Genotyping were performed by Taqman allelic discrimination. T carriers of rs1501299 had a higher BMI reduction (b*=0.28±0.12; p=1.70.10-2) and TT genotype of rs12086634 influence on AC reduction (b*=-0.33±0.13; p=1.24.10-2), independent of sex, age and modality of physical exercise. Ultimately, we observed an association of SNP of ADIPOQ and HSD11β1 gene with anthropometric variables early in life and the importance of physical exercise on biochemical and obesity related features.La obesidad ha sobrecargado el sistema de salud pública y es una característica multifactorial. Este estudio tuvo como objetivo verificar si los polimorfismos de nucleótido único (SNP) en los genes ADIPOQ (rs1501299) y HSD11β1 (rs12086634) influyen en los resultados antropométricos y bioquímicos (Índice de Masa Corporal (IMC), Circunferencia Abdominal (CA), Lipoproteínas de Baja Densidad (LDL-C), Lipoproteínas de Alta Densidad (HDL-C), Triglicéridos (TG), Colesterol Total (TC) y Glucosa (Glu)) antes y después de practicar diferentes tipos de ejercicios físicos en una muestra de 126 niños y adolescentes brasileños. Los SNPs fueron idenficados mediante discriminación alélica usando sondas Taqman. Los portadores del alelo T del polimofismo rs1501299 del gen ADIPOQ tuvieron una mayor reducción del IMC (b*=0,28±0,12; p=1,70.10-2) y el genotipo TT del polimorfismo rs12086634 del gen HSD11β1 influencia en la reducción de AC (b*=-0,33±0,13; p=1,24.10-2), independiente de sexo, edad y modalidad de ejercicio físico. Por fin, observamos una asociación entre los SNPs de los genes ADIPOQ y HSD11β1 con variables antropométricas en las primeras etapas de la vida, así como la importancia del ejercicio físico sobre características bioquímicas y relacionadas con la obesidad.Obesity have overloaded the public health system and it is considered a multifactorial trait. This study aimed to verify if Single Nucleotide Polymorphisms (SNP) in ADIPOQ (rs1501299) and HSD11β1 (rs12086634) genes influence the anthropometric and biochemical outcomes (Body Mass Index (BMI), Abdominal Circumference (AC), Low Density Lipoprotein (LDL-C), High Density Lipoprotein (HDL-C), Triglycerides (TG), Total Cholesterol (TC) and Glucose (Glu)) before and after practicing physical exercises training modalities, in a sample of 126 Southern Brazilian children and adolescents. Genotyping were performed by Taqman allelic discrimination. T carriers of rs1501299 had a higher BMI reduction (b*=0.28±0.12; p=1.70.10-2) and TT genotype of rs12086634 influence on AC reduction (b*=-0.33±0.13; p=1.24.10-2), independent of sex, age and modality of physical exercise. Ultimately, we observed an association of SNP of ADIPOQ and HSD11β1 gene with anthropometric variables early in life and the importance of physical exercise on biochemical and obesity related features