Abstract The choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are fundamental to neurophysiological functions of the central cholinergic system. We confirmed and quantified the presence of extracellular ChAT protein in human plasma and also characterized ChAT and VAChT polymorphisms, protein and activity levels in plasma of Alzheimer's disease patients (AD; N = 112) and in cognitively healthy controls (EC; N = 118). We found no significant differences in plasma levels of ChAT activity and protein between AD and EC groups. Although no differences were observed in plasma ChAT activity and protein concentration among ChEI-treated and untreated AD patients, ChAT activity and protein levels variance in plasma were higher among the rivastigmine-treated group (ChAT protein: p = 0.005; ChAT activity: p = 0.0002). Moreover, AD patients homozygous for SNP rs1880676 A allele exhibited higher levels of ChAT activity. Considering this is the first study to report the influence of genetic variability of CHAT locus over ChAT activity in AD patients plasma, it opens a new set of important questions on peripheral cholinergic signaling in AD.

Abstract ATP-Binding Cassette (ABC) transporters are involved in cholesterol metabolism and their dysfunctions could lead to obesity-associated complications. It was investigated whether SNPs in the ABCA1 (rs1800977 and rs2230806), ABCA7 (rs2279796) and ABCG1 (rs692383 and rs3827225) genes can modulate the responsiveness of 137 obese women to a weight-loss dietary intervention. Thus, anthropometric and lipid profiles were collected at baseline and after nine weeks of a calorie-restricted diet of 600kcal per day and participants were genotyped for the ABC genes SNPs. Regarding the transversal analysis, the ABCA7 rs2279796 GG genotype was associated with higher levels of total cholesterol and LDL-c at baseline (p = 0.044 for both). Association between ABCG1 rs692383 AA genotype and lower BMI were found in the post-diet moment, however, statistical significance was lost after multi-test correction. Regarding the longitudinal analysis, after multi-test correction, the association remained between ABCG1 rs692383 G allele and HDL-c levels: G allele carriers had a lower HDL-c reduction (p = 0.043). Results suggest the standard weight-loss diet applied in this study could attenuate the ABCA7 rs2279796 GG genotype effects found at baseline and non-dyslipidemic obese women with ABCG1 rs692383 G allele are benefitting from the diet with a lower reduction in HDL-c levels.

RESUMO Introdução: Estudos de associação entre a obesidade e fatores genéticos têm demonstrado a significativa contribuição de polimorfismos relacionados à distribuição de gordura corporal e processo inflamatório subclínico. Objetivo: Investigar a associação entre os genótipos do polimorfismo Gln27Glu do gene ADRB2 e indicadores de adiposidade, marcadores inflamatórios, parâmetros metabólicos e de aptidão física em adolescentes com excesso de peso. Métodos: Participaram 44 adolescentes, de ambos os sexos, com idade entre 13 e 17 anos, com diagnóstico clínico positivo de excesso de peso, divididos em dois grupos conforme os genótipos do polimorfismo Gln27Glu do gene ADRB2: a) Grupo de portadores do alelo 27Glu (Gln27Glu/Glu27Glu) (n=22); b) Grupo de não portadores do alelo 27Glu (Gln27Gln) (n=22). Ambos os grupos foram avaliados quanto à composição corporal, maturação sexual, variáveis de aptidão cardiorrespiratória e indicadores de força muscular. Foram dosados glicemia e insulina basais, perfil lipídico e perfil inflamatório. As adiposidades abdominais subcutânea e visceral foram avaliadas através de ultrassonografia. A genotipagem do polimorfismo Gln27Glu do gene ADRB2 foi realizada através do ensaio de discriminação alélica Taqman. Resultados: A frequência genotípica encontrada foi: Gln/Gln (n=22) (50,0%), Gln/Glu (n=18) (41,0%) e Glu/Glu (n=4) (9,0%). A frequência do alelo do 27Glu foi de 29,5%. O grupo de adolescentes portadores do alelo 27Glu do gene ADRB2 apresentou maiores médias de indicadores de adiposidade (circunferência abdominal, massa gorda troncular e gordura visceral), assim como menores concentrações de IL-10 quando comparados aos não portadores. Conclusões: O alelo 27Glu apresentou associação com os indicadores de adiposidade em adolescentes com excesso de peso, assim como a gordura abdominal subcutânea demonstrou relação inversa com as variáveis inflamatórias e o consumo máximo de oxigênio, podendo resultar em maiores prejuízos à saúde. Nível de evidência III; Estudo de caso-controle.

ABSTRACT Introduction: Studies of association between obesity and genetic factors have demonstrated a significant contribution of polymorphisms related to body fat distribution and subclinical inflammatory process. Objective: To investigate the association between genotypes of the Gln27Glu polymorphism of the ADRB2 gene and indicators of adiposity, inflammatory markers, metabolic parameters and parameters of physical fitness in overweight adolescents. Methods: A total of 44 male and female adolescents, aged between 13 and 17 years, with positive clinical diagnosis of overweight, were divided into two groups according to the Gln27Glu polymorphism genotypes of the ADRB2 gene: a) Group of carriers of the 27Glu allele (Gln27Glu/Glu27Glu) (n = 22); b) Group of non-carriers of the 27Glu allele (Gln27Gln) (n = 22). Both groups were evaluated for body composition, sexual maturation, cardiorespiratory fitness variables and indicators of muscle strength. Basal glycemia and insulin, lipid profile and inflammatory profile were measured. Abdominal subcutaneous and visceral adiposities were evaluated by ultrasonography. Genotyping of the Gln27Glu polymorphism of the ADRB2 gene was performed by the Taqman allelic discrimination assay. Results: The genotype frequency found was: Gln/Gln (n = 22) (50.0%), Gln/Glu (n = 18) (41.0%) and Glu/Glu (n = 4) %). The frequency of the 27Glu allele was 29.5%. The group of adolescent carriers of the 27Glu allele of the ADRB2 gene presented higher mean adiposity indicators (abdominal circumference, trunk fat mass and visceral fat), as well as lower IL-10 concentrations when compared to non-carriers. Conclusions: The 27Glu allele was associated with adiposity indicators in overweight adolescents, while subcutaneous abdominal fat exhibited an inverse relationship with inflammatory variables and maximum oxygen uptake, which may result in more damage to health. Level of evidence III; Case-control study.

RESUMEN Introducción: Estudios de asociación entre la obesidad y factores genéticos han demostrado la significativa contribución de polimorfismos relacionados a la distribución de grasa corporal y proceso inflamatorio subclínico. Objetivo: Investigar la asociación entre los genotipos del polimorfismo Gln27Glu del gen ADRB2 e indicadores de adiposidad, marcadores inflamatorios, parámetros metabólicos y de aptitud física en adolescentes con exceso de peso. Métodos: Participaron 44 adolescentes, de ambos sexos, con edad entre 13 y 17 años, con diagnóstico clínico positivo de exceso de peso, divididos en dos grupos según los genotipos del polimorfismo Gln27Glu del gen ADRB2: a) Grupo de portadores del alelo 27Glu (Gln27Glu/Glu27Glu) (n = 22); b) Grupo de no portadores del alelo 27Glu (Gln27Gln) (n = 22). Ambos grupos fueron evaluados cuanto a la composición corporal, madurez sexual, variables de aptitud cardiorrespiratoria e indicadores de fuerza muscular. Fueron dosificadas glucemia e insulina basales, perfil lipídico y perfil inflamatorio. Las adiposidades abdominales subcutánea y visceral fueron evaluadas a través de ultrasonografía. El genotipado del polimorfismo Gln27Glu del gen ADRB2 fue realizado a través del ensayo de discriminación alélica Taqman. Resultados: La frecuencia genotípica encontrada fue: Gln/Gln (n = 22) (50,0%), Gln/Glu (n = 18) (41,0%) y Glu/Glu (n = 4) (9,0%). La frecuencia del alelo del 27Glu fue del 29,5%. El grupo de adolescentes portadores del alelo 27Glu del gen ADRB2 presentó mayores promedios de indicadores de adiposidad (circunferencia abdominal, masa grasa troncular y grasa visceral), así como menores concentraciones de IL-10, en comparación con los no portadores. Conclusiones: El alelo 27Glu presentó asociación con los indicadores de adiposidad en adolescentes con exceso de peso, así como la grasa abdominal subcutánea demostró relación inversa con las variables inflamatorias y el consumo máximo de oxígeno, lo que puede resultar en mayores perjuicios a la salud. Nivel de Evidencia III; Estudio de caso-control.

Abstract Genes can influence lipid profile and anthropometric variables related to obesity. The present study aimed to verify if variants of the APOE, APOB, ADIPOQ, HSD11β1, and PLIN4 genes are associated with lipid levels or anthropometric variables in a sample comprised of 393 Euro-Brazilian children and adolescents. DNA was genotyped by TaqMan allelic discrimination assay. The ε4 and ε2 alleles of the APOE gene were associated respectively with lower high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels (p=0.015 and p=0.012, respectively), while the ε3 allele was associated with higher abdominal circumference (p=0.0416) and excess weight (p=0.0001). The G allele (rs846910) of the HSD11β1 gene was also associated with excess weight (p=0.039). No other association was found. Our results indicate that the ε4 and ε2 alleles could contribute to lower HDL-C and LDL-C levels, respectively, furthermore, the ε3 allele and the G allele (rs846910) of HSD11β1 gene may be risk factors for excess of weight.These findings are very important because we observed that some genetic variants influence the lipid profile and anthropometric variables early in life.

Resumo Objetivo: Analisar a associação entre o polimorfismo Trp64Arg do gene ADRB3, as taxas de oxidação máxima de gorduras e as concentrações do perfil lipídico em adolescentes não obesos. Métodos: Participaram do estudo 72 escolares, de ambos os sexos, com idade entre 11 e 17 anos. Foram avaliadas as variáveis antropométricas e de composição corporal, além do colesterol total, lipoproteina de alta densidade, lipoproteina de baixa densidade, triglicerídeos; insulina e glicemia basal. A amostra foi dividida em dois grupos, segundo a presença ou não do polimorfismo: não portadores do alelo Arg64, ou seja, homozigotos (Trp64Trp: n = 54) e portadores do alelo Arg64 (Trp64Arg + Arg64Arg: n = 18), em que a frequência do alelo Arg64 foide 15,2%. O consumo máximo de oxigênio e pico de consumo máximo de oxigênio durante o exercício foram obtidos por meio do teste aeróbio submáximo de sintoma limitado em esteira. A oxidação máxima de gorduras foi determinada de acordo com a razão de trocas ventilatórias propostas na Tabela de Lusk. Resultados: Os adolescentes portadores do alelo menos frequente (Trp64Arg e Arg64Arg) apresentaram maiores concentrações de lipoproteina de baixa densidade (p = 0,031) e menores taxasde oxidação máxima de gorduras (p = 0,038) quando comparados aos não portadores (Trp64Trp). Conclusões: Embora os processos fisiológicos relacionados à lipólise e ao metabolismo de lipídeos sejam complexos, a presença do alelo Arg64 associou-se a menores taxas de FATMAX durante exercício aeróbio, bem como maiores níveis de lipoproteina de baixa densidade em adolescentes.

Abstract Objective: To analyze the association between the Trp64Arg polymorphism of the ADRB3 gene, maximal fat oxidation rates and the lipid profile levels in non-obese adolescents. Methods: 72 schoolchildren, of both genders, aged between 11 and 17 years, participated in the study. The anthropometric and body composition variables, in addition to total cholesterol, HDL-c, LDL-c, triglycerides, insulin, and basal glycemia, were evaluated. The sample was divided into two groups according to the presence or absence of the polymorphism: non-carriers of the Arg64 allele, i.e., homozygous (Trp64Trp: n = 54), and carriers of the Arg64 allele (Trp64Arg + Arg64Arg: n = 18), in which the frequency of the Arg64 allele was 15.2%. The maximal oxygen uptake and peak of oxygen uptake during exercise were obtained through the symptom-limited, submaximal treadmill test. Maximal fat oxidation was determined according to the ventilatory ratio proposed in Lusk's table. Results: Adolescents carrying the less frequent allele (Trp64Arg and Arg64Arg) had higher LDL-c levels (p = 0.031) and lower maximal fat oxidation rates (p = 0.038) when compared with non-carriers (Trp64Trp). Conclusions: Although the physiological processes related to lipolysis and lipid metabolism are complex, the presence of the Arg 64 allele was associated with lower rates of FATMAX during aerobic exercise, as well as with higher levels of LDL-c in adolescents.

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.

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.

ABSTRACT Aim To compare the anthropometric, metabolic, and inflammatory parameters of overweight adolescents after 12-weeks of resistance and aerobic training (CT), taking into account the Gln27Glu polymorphism of the β2 adrenergic receptor (ADRB2) gene. Methods Forty-seven adolescents (15.05±1.07y) were assigned to one of four groups, according to the presence or absence of the Glu27 allele: CT (CarrierT n=11; NoncarrierT n=11) or control (CarrierC n=13; NoncarrierC n=12). Body composition, abdominal fat, maturation, fitness, metabolic and lipid profile, inflammatory markers were assessed. The CT consisted of six resistance exercises, followed by 30 min of walking/running at 50-80% VO2max, totaling 60 min/session, three times a week. A mixed-model factorial ANOVA was used to compare variables at baseline and after 12-weeks. Results TC was effective in reducing total fat mass (NoncarrierT ES=.45, CarrierT ES=.27) and subcutaneous abdominal fat (NoncarrierT ES=.48, CarrierT ES=.46) and increasing lean mass (NoncarrierT ES=.58, CarrierT ES=.60) and fitness. CarrierT group showed a reduction in leptin (ES=.49). Conclusion The responses of body composition and physical fitness to TC were not influenced by the presence of the Gln27Glu polymorphism. However, only the Glu27 allele carriers showed reductions in leptin after 12-weeks. Besides, a lack of intervention caused obesogenic effects, especially in Glu27carriers.

Resumo Objetivo: Determinar a influência dos polimorfismos dos receptores adrenérgicos beta 2 (ADRB2) no desencadeamento de broncoespasmo induzido pelo exercício (BIE) em adolescentes. Métodos: Os sujeitos foram divididos em dois grupos: BIE presente (BIE+) (n=45) e BIE ausente (BIE−) (n=115). O teste de broncoprovocação com exercício foi feito com protocolo que consistiu em caminhar/correr durante no mínimo oito minutos em intensidade superior a 85% da frequência cardíaca máxima, considerando como BIE presente uma queda de 10% do volume expiratório forçado no primeiro segundo (VEF1). A genotipagem do gene ADRB2 foi feita pelo método Taqman por meio do aparelho Step One Plus. Para análise estatística usaram-se os testes t independente, U de Mann-Whitney, qui-quadrado e coeficiente de correlação de Spearman. Resultados: Idade, massa corporal, estatura, VEF1, CVF e relação VEF1/CVF foram menores no grupo BIE+ em comparação com o BIE− (p<0,05). Não houve diferenças significativas na proporção do alelo na posição 27 e dos genótipos Arg16Gly e Gln27Glu entre os grupos BIE+ e BIE− (p=0,26; p=0,97 e p=0,43, respectivamente). Entretanto, verificou-se uma tendência à significância estatística na maior proporção do alelo Gly16 para o grupo BIE+ comparado com o BIE− (p=0,08). Conclusões: A presença de polimorfismos associados ao alelo Glu27 e os genótipos Arg16Gly e Gln27Glu não influenciam no BIE. Porém, a tendência estatística observada para uma maior frequência do alelo Gly16 nos indivíduos com a presença de BIE pode ser considerado indício da influência de polimorfismos no gene ADBR2 no BIE em adolescentes.

Abstract Objective: To determine the influence of polymorphisms of the beta-2 adrenergic receptor (ADRB2) in triggering exercise-induced bronchospasm (EIB) in adolescents. Methods: The subjects were divided into two groups: present EIB (EIB+) (n=45) and absent EIB (EIB−) (n=115). The bronchial provocation test with exercise was performed with a protocol that consisted of walking/running for at least eight minutes at high intensity, i.e., >85% of maximum heart rate, considering EIB+ as a 10% decrease in forced expiratory volume in one second (FEV1). The genotyping of the ADRB2 gene was performed by the Taqman method, using the Step One Plus system. Independent t-test, Mann–Whitney and Chi-square tests, as well as Spearman's correlation coefficient were used for the statistical analysis. Results: Age, body weight, height, FEV1, FVC and FEV1/FVC ratio were lower in the EIB+ group when compared to EIB− (p<0.05). There were no significant differences in the proportion of the allele at position 27 and Arg16Gly and Gln27Glu genotypes between the EIB+ and EIB− groups (p=0.26; p=0.97 and p=0.43, respectively). However, there was a trend toward statistical significance regarding the greater proportion of the Gly16 allele for the EIB+ when compared to the EIB− group (p=0.08). Conclusions: The presence of polymorphisms associated with the Glu27 allele and Arg16Gly and Gln27Glu genotypes had no influence on EIB. However, the statistical trend toward greater frequency of the Gly16 allele in individuals with EIB+ can be considered evidence of the influence of polymorphisms of the ADBR2 gene on EIB in adolescents.

Objetivo: Investigar a associação dos polimorfismos Arg16Gly e Gln27Glu do gene receptor β2-adrenérgico (ADRB2) com a ocorrência de asma e sobrepeso, bem como a influência do gene sobre variáveis antropométricas, clínicas, bioquímicas e de aptidão física em crianças e adolescentes. Métodos: Os indivíduos foram avaliados quanto à frequência alélica do gene ADRB2, estatura, peso, índice de massa corporal, IMC-escore Z, circunferência abdominal, estágio puberal, frequência cardíaca de repouso, pressão arterial, colesterol total, glicose, insulina, lipoproteína de alta densidade, lipoproteína de baixa densidade, triglicerídeos, Homeostasis Metabolic Assessment (HOMA2-IR), Quantitative Insulin Sensitivity Check Index (QUICKI) e consumo máximo de oxigênio (VO2max). Os participantes foram divididos em quatro grupos: sobrepeso asmático (n=39), sobrepeso não asmático (n=115), peso normal asmático (n=12) e peso normal não asmático (n=40). Resultados: Com relação ao polimorfismo Gln27Glu, foi observado maior valor de colesterol total nos indivíduos do genótipo usual do que naqueles que carregam a variante (p=0,04). Não foi encontrada evidência de que os polimorfismos avaliados influenciem a aptidão física. O alelo Arg16 foi encontrado em maior frequência no grupo de peso normal asmático comparado com o grupo de peso normal não asmático (p=0,02) e o alelo Glu27 foi mais frequentemente encontrado no grupo de sobrepeso asmático comparado com o grupo de peso normal não asmático (p=0,03). Conclusões: A associação do alelo Arg16 com a ocorrência de asma e a associação do alelo Glu27 com adolescentes com sobrepeso asmáticos evidenciam a contribuição do gene ADBR2 para o desenvolvimento da obesidade e da asma.

Objective: To investigate the association of Arg16Gly and Gln27Glu polymorphisms of β2-adrenergic receptor gene (ADRB2) with the occurrence of asthma and overweight and the gene's influence on anthropometric, clinic, biochemical and physical fitness variables in children and adolescents. Methods: Subjects were evaluated for allelic frequencies of the β2-adrenergic receptor gene, height, weight, body mass index (BMI), BMI Z-score, waist circumference (WC), pubertal stage, resting heart rate (HRres), blood pressure (BP), total cholesterol (TC), glucose, insulin, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), triglyceride (TG), Homeostasis Metabolic Assessment (HOMA2-IR), Quantitative Insulin Sensitivity Check Index (QUICKI) and maximal oxygen uptake (VO2max). The participants were divided in four groups: overweight asthmatic (n=39), overweight non-asthmatic (n=115), normal weight asthmatic (n=12), and normal weight non-asthmatic (n=40). Results: Regarding the Gln27Glu polymorphism, higher total cholesterol was observed in usual genotype individuals than in genetic variant carriers (p=0.04). No evidence was found that the evaluated polymorphisms are influencing the physical fitness. The Arg16 allele was found more frequently among the normal weight asthmatic group when compared to the normal weight non-asthmatic group (p=0.02), and the Glu27 allele was more frequently found in the overweight asthmatics group when compared to the normal weight non-asthmatic group (p=0.03). Conclusions: The association of Arg16 allele with the occurrence of asthma and of the Glu27 allele with overweight asthmatic adolescents evidenced the contribution of the β2-adrenergic receptor gene to the development of obesity and asthma.

O objetivo desta revisão foi apresentar os genes APOE e MAPT e as proteínas ApoE e tau como marcadores genéticos que vêm sendo estudados na demência frontotemporal com inclusões tau-positivas, os quais poderão, futuramente, auxiliar no diagnóstico diferencial. A demência frontotemporal é um transtorno neurocognitivo marcado por disfunção dos lobos frontais e temporais, geralmente associada à atrofia dessas estruturas e relativa preservação das regiões cerebrais posteriores. Clinicamente, manifesta-se por volta dos 57 anos de idade, com igual incidência entre homens e mulheres. A demência frontotemporal tem início insidioso e caráter progressivo, com discreto comprometimento da memória episódica, mas com importantes alterações comportamentais, de personalidade e na linguagem. Devido às semelhanças possíveis entre as manifestações clínicas das demências inclusive a doença de Alzheimer, há grande dificuldade no diagnóstico diferencial, sendo necessário um exame clínico e neuropsicológico detalhado do indivíduo acometido, além de exames bioquímicos e de neuroimagem. O gene MAPT codifica a proteína tau e sua função principal é estabilizar os microtúbulos. Em células nervosas sadias, a proteína tau é normalmente encontrada nos axônios, ao contrário dos achados descritos nos transtornos neurocognitivos, em que a proteína se encontra distribuída no corpo celular e nos dendritos. A apolipoproteína E ApoE é uma glicoproteína polimórfica, codificada pelo gene APOE, que tem importante papel na absorção, transporte e redistribuição de colesterol, necessário ao reparo e manutenção do tecido nervoso. Com o aumento da expectativa de vida e controle da natalidade, o envelhecimento populacional tornou-se fato, trazendo consigo maior prevalência de doenças crônico-degenerativas, de modo que é de extrema importância conhecer melhor essas doenças, no sentido de buscar novas formas de tratamento, visto que as demências não dispõem ainda de cura. Sabe-se que o diagnóstico definitivo da maioria das síndromes demenciais depende do exame neuropatológico, mas conclui-se que, com o avanço tecnológico, bem como técnicas de biologia e genética molecular, novas perspectivas têm surgido para o diagnóstico diferencial e precoce das demências.

This review aimed to present the APOE and MAPT gene and ApoE and tau proteins as genetic markers that have been studied in frontotemporal dementia, which may in future help in the differential diagnosis. Frontotemporal dementia is a neurocognitive disorder characterized by frontal and temporal lobes dysfunction, often associated with atrophy of these structures and relative preservation of posterior brain regions. Clinically, it manifests around 57 years-old, with same incidence in men and women. Frontotemporal dementia has an insidious and progressive onset, with a mild impairment of episodic memory, but with significant behavioral, personality and language changes. Due to possible similarities between the clinical manifestations of dementia including Alzheimer's disease there is a great difficulty in the differential diagnosis, which needs detailed clinical and neuropsychological examination of individuals affected, further biochemical and neuroimaging exams. MAPT gene encodes tau protein, its main function is to stabilize microtubules. In healthy nerve cells, tau protein is usually found in the axons, in contrast to the findings described in neurocognitive disorders in which protein is distributed in the cell body and dendrites. The apolipoprotein E ApoE is a polymorphic glycoprotein, encoded by the APOE gene, which plays an important role in absorption, transport and redistribution of cholesterol, necessary for the repair and maintenance of nervous tissue. Because of increasing life expectancy and birth control, population aging has become fact, bringing a higher prevalence of chronic diseases, so it is extremely important to know more about these dis eases, in order to seek new ways of treating dementias seen that do not have a cure. It is known that the definitive diagnosis of most dementia depends on neuropathological examination, however, with technological advances and techniques of molecular biology and genetics, new opportunities have emerged for the early and differential diagnosis of dementias.

In this study, we investigated the influence of two SNPs (rs846910 and rs12086634) of the HSD11B1 gene that encodes 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1), the enzyme that catalyzes the conversion of cortisol to cortisone, on variables associated with obesity and metabolic syndrome in 215 individuals of both sexes from southern Brazil. The HSD11B1 gene variants were genotyped using the TaqMan SNP genotyping assay. Glucose, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol were measured by standard automated methods. Significant results were found in women, with carriers of the G allele of SNP rs12086634 having higher glucose levels than non-carriers. Carriers of the A allele of SNP rs846910 had higher levels of HDL-cholesterol. The involvement of both polymorphisms as independent factors in determining the levels of glucose and HDL-cholesterol was confirmed by multiple regression analysis (β = 0.19 ± 0.09, p = 0.03 and β = 0.22 ± 0.10, p = 0.03, respectively). Our findings suggest that the HSD11B1SNPs studied may indirectly influence glucose and HDL-cholesterol metabolism in women, possibly through down-regulation of the HSD11B1 gene by estrogen.

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.

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 x 2) were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES). The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001), for high and low SES (p < 0.05) and mainly for participants with 30-49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018) and the 30-39 y (p = 0.036) groups, suggesting a role for this polymorphism related to BMI control.

OBJETIVO: Avaliar o efeito de 12 semanas de exercícios físicos em variáveis associadas a fatores de risco cardiovascular e na atividade da butirilcolinesterase (BChE) em adolescentes obesos. SUJEITOS E MÉTODOS: A amostra foi composta por 24 obesos e 51 eutróficos controles. Inicialmente e após 12 semanas foram avaliados: peso, estatura, IMC, circunferência abdominal (CA), percentual de gordura (%G), consumo máximo de oxigênio (VO2máx), pressão arterial sistólica (PAS) e diastólica (PAD), glicemia (GLI) e insulinemia (INS) basal e após 120 min, triacilglicerol (TG), colesterol total (CT), colesterol LDL, colesterol HDL e a atividade da BChE (kU/l). RESULTADOS: Após a intervenção, houve redução significativa no IMC, CA, %G, PAD, PAD, TG, GLI 120, INS, INS 120 min e na atividade da BChE. CONCLUSÃO: A redução da atividade da BChE, observada após a intervenção, foi acompanhada da redução de variáveis associadas a risco cardiovascular e à obesidade, indicando que a BChE pode ser utilizada como marcador secundário para os riscos associados à obesidade precoce.

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.