RESUMO
BACKGROUND: Central Illustration : G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. BACKGROUND: Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. OBJECTIVE: To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. METHOD: The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. RESULTS: The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). CONCLUSION: These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.
Assuntos
Proteínas Heterotriméricas de Ligação ao GTP , Hipertensão , Humanos , Alelos , Pressão Sanguínea/genética , Brasil , Genótipo , Hipertensão/genética , Subunidades Proteicas/genética , Proteínas Heterotriméricas de Ligação ao GTP/genéticaRESUMO
Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.
Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.
RESUMO
Abstract Objective: Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance. Methods: This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects. Results: As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies. Conclusion: The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed.
Resumo Objetivo A obesidade é uma doença crônica sustentada por fatores ambientais e genéticos. Estudos epidemiológicos documentaram que maior ingestão de energia e um estilo de vida sedentário, bem como a contribuição genética, são forças por trás da epidemia de obesidade. O conhecimento sobre a interação entre os componentes genéticos e ambientais pode facilitar a escolha das medidas mais efetivas e específicas para a prevenção da obesidade. O objetivo deste estudo foi avaliar a relação entre os genes associado à massa de gordura e à obesidade (FTO), homólogo 1 do oncogene viral v-akt de timoma murino (AKT1) e de ligação AKT1 (AKTIP) e a obesidade infantil e a resistência à insulina. Métodos Estudo de caso-controle no qual os polimorfismos de nucleotídeo simples (SNPs) nos genes FTO (rs99396096), AKT1 e AKTIP foram genotipados em grupos de controle e de crianças obesas/acima do peso. Foram recrutadas 195 crianças obesas/acima do peso e 153 indivíduos controle. Resultados Como esperado, os indivíduos do grupo obeso/acima do peso apresentaram maior índice de massa corporal, maior glicemia de jejum, índice do modelo de avaliação de homeostase (HOMA-IR), colesterol total, lipoproteína de baixa densidade e triglicerídeos. Contudo, não encontramos diferenças significativas no genótipo de polimorfismos gênicos ou nas frequências alélicas. Conclusão Nossos resultados sugerem que os polimorfismos AKT1, FTO e AKTIP não estavam associados à obesidade/sobrepeso em crianças brasileiras. São necessários estudos futuros sobre a genética da obesidade em crianças brasileiras e suas interações ambientais.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Proteínas Adaptadoras de Transdução de Sinal/genética , Sobrepeso/genética , Proteínas Reguladoras de Apoptose/genética , Obesidade Pediátrica/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Brasil/etnologia , Resistência à Insulina , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Frequência do Gene/genéticaRESUMO
Increased matrix metalloproteinase (MMP)-2 is implicated in the vascular remodeling of hypertension. Calponin-1 is a contractile protein, and its absence is associated with vascular smooth muscle cell (VSMC) phenotype switch, which leads to migration and remodeling. We evaluated whether increased MMP-2 activity precedes chronic vascular remodeling by decreasing calponin-1 and inducing VSMC proliferation. Sham or two kidney-one clip (2K1C) rats were treated with doxycycline at 30mg/kg/day. Systolic blood pressure was increased in the 2K1C rats after 1 and 2weeks post-surgery, and doxycycline was effective to reduce it only at 2weeks of hypertension (p<0.05). Increased activity of MMP-2 was observed in aortas from 2K1C at 1 and 2weeks of hypertension, followed by increased VSMC proliferation, and those effects were abolished by treating 2K1C rats with doxycycline (p<0.05). Increased aortic media to lumen ratio started to emerge in 2K1C rats at 1week of hypertension, and it was established by 2weeks. MMP-2 and calponin-1 co-localized in the cytosol of VSMC. Aortas from 2K1C rats showed a significant reduction in calponin-1 levels at 1week of hypertension, and doxycycline prevented its loss (p<0.05). However, at 2weeks of hypertension, calponin-1 was upregulated in 2K1C (p<0.05 vs. Sham groups). The mRNA levels of calponin-1 were not altered in the aortas of 2K1C at 1week of hypertension. MMP-2 may contribute to the post-translational decrease in calponin-1, thus culminating in hypertension-induced maladaptive arterial remodeling.
Assuntos
Artérias/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Endotélio Vascular/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Proteínas dos Microfilamentos/metabolismo , Músculo Liso Vascular/metabolismo , Pré-Hipertensão/metabolismo , Remodelação Vascular , Animais , Aorta , Artérias/enzimologia , Artérias/patologia , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proliferação de Células , Citosol/enzimologia , Citosol/metabolismo , Citosol/patologia , Progressão da Doença , Endotélio Vascular/enzimologia , Endotélio Vascular/patologia , Regulação da Expressão Gênica , Masculino , Proteínas dos Microfilamentos/genética , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Proteínas Nucleares/metabolismo , Pré-Hipertensão/patologia , Pré-Hipertensão/fisiopatologia , Proteólise , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Wistar , Transativadores/metabolismoRESUMO
OBJECTIVE: Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance. METHODS: This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects. RESULTS: As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies. CONCLUSION: The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed.
