RESUMO
BACKGROUND: Obesity is defined as a multifactorial disease, marked by excessive accumulation of body fat, responsible for compromising the individual's health over the years. The energy balance is essential for the proper functioning of the body, as the individual needs to earn and spend energy in a compensatory way. Mitochondrial Uncoupling Proteins (UCP) help in energy expenditure through heat release and genetic polymorphisms could be responsible for reducing energy consumption to release heat and consequently generate an excessive accumulation of fat in the body. Thus, this study aimed to investigate the potential association between six UCP3 polymorphisms, that have not yet been represented in ClinVar®, and pediatric obesity susceptibility. METHODS: A case-control study was conducted with 225 children from Central Brazil. The groups were subdivided into obese (123) and eutrophic (102) individuals. The polymorphisms rs15763, rs1685354, rs1800849, rs11235972, rs647126, and rs3781907 were determined by real-time Polymerase Chain Reaction (qPCR). RESULTS: Biochemical and anthropometric evaluation of obese group showed higher levels of triglycerides, insulin resistance, and LDL-C and low level of HDL-C. Insulin resistance, age, sex, HDL-C, fasting glucose, triglyceride levels, and parents' BMI explained up to 50% of body mass deposition in the studied population. Additionally, obese mothers contribute 2 × more to the Z-BMI of their children than the fathers. The SNP rs647126 contributed to 20% to the risk of obesity in children and the SNP rs3781907 contribute to 10%. Mutant alleles of UCP3 increase the risk for triglycerides, total cholesterol, and HDL-C levels. The polymorphism rs3781907 is the only one that could not be a biomarker for obesity as the risk allele seem to be protective gains the increase in Z-BMI in our pediatric population. Haplotype analysis demonstrated two SNP blocks (rs15763, rs647126, and rs1685534) and (rs11235972 and rs1800849) that showed linkage disequilibrium, with LOD 76.3% and D' = 0.96 and LOD 57.4% and D' = 0.97, respectively. CONCLUSIONS: The causality between UCP3 polymorphism and obesity were not detected. On the other hand, the studied polymorphism contributes to Z-BMI, HOMA-IR, triglycerides, total cholesterol, and HDL-C levels. Haplotypes are concordant with the obese phenotype and contribute minimally to the risk of obesity.
Assuntos
Resistência à Insulina , Obesidade Infantil , Proteína Desacopladora 3 , Criança , Humanos , Índice de Massa Corporal , Estudos de Casos e Controles , Colesterol , Frequência do Gene , Genótipo , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos , Proteína Desacopladora 3/genéticaRESUMO
The present study compared the gene expression pattern of some previously described genes at the time of diagnosis and after induction chemotherapy for childhood acute lymphoblastic leukemia (ALL) in patients submitted to Brazilian Childhood Leukemia Treatment Group (GBTLI) ALL-99 Protocol. Samples were obtained at the time of diagnosis from 16 patients with ALL and on the 28th day of induction chemotherapy the bone marrow samples were obtained from 12 children. The genes expression profiles in diagnostic and induction samples were analyzed by array-based qPCR and then related to the clinical and biological prognostic factors. The results showed significant associations (p ≤ 0.05) between gender and immunophenotype, immunophenotype and age, immunophenotype and risk group, presence of CD10 and RUNX1 expression, risk group, and immunophenotype. A significant positive correlation was observed between the expression levels of BAX and BCL2. There was a significant difference (p = 0.008) between the gene expression pattern at the time of diagnosis and after induction chemotherapy. The expression pattern of these genes after the induction phase of treatment approached the expression profile of the control group, indicating a good induction response in children treated according to the GBTLI ALL-99 protocol. The findings of the current research could be routinely useful for clinical practice and could assist in the discovery phase of medical applications.
Assuntos
Regulação Neoplásica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Transcriptoma , Proteína X Associada a bcl-2/biossínteseRESUMO
To assess genetic structure and phenotypic diversity of Eupemphix nattereri Steindachner, 1863, morphometric and molecular analyses were carried out for nine populations from the State of Goiás. A total of 11 morphometric traits were evaluated and genetic information was estimated using RAPD markers. Genetic and phenotypic distances were determined as a function of geographical origin. Correlation among genetic, morphometric, micro, and macroenviromental were analyzed by the Mantel test. Genetic data indicated high levels of genetic diversity (st= 0.3) among the nine populations. Mantel tests did not reveal a significant positive correlation between genetic and geographical distances, indicating that locally geographical populations were not genetically similar, even in distances smaller than 50 km. Discriminant analysis on 11 morphometric measurements showed a high divergence among the nine populations. However, a marginally significant correlation (P=0.08) between genetic and morphometric distances was found. The observed correlation was not causal in terms of the relationship between phenotype and genotype, but indicated common spatial structures. Thus, our results suggest that isolation-by-distance processes may explain population divergence in Eupemphix nattereri.
Visando conhecer a estrutura genética e a diversidade fenotípica da espécie Eupemphix nattereri Steindachner, 1863, análises morfométricas e moleculares foram realizadas em nove populações do Estado de Goiás. Onze caracteres morfométricos foram avaliados e a diversidade genética foi estimada com o uso de marcadores RAPD. As matrizes de distâncias genéticas e fenotípicas foram correlacionadas com as distâncias geográficas e dados macro e microambientais, utilizando o teste de Mantel. Em relação aos caracteres genéticos, foram encontrados altos níveis de diversidade (st= 0,3) entre as nove populações. Não houve, entretanto, uma correlação positiva significativa entre as distâncias genéticas e geográficas, indicando que populações geograficamente próximas não seriam geneticamente similares, mesmo estando situadas entre distâncias menores do que 50 km. Uma análise discriminante dos onze caracteres morfométricos evidenciou também uma elevada divergência entre as nove populações. Entretanto, foi encontrada uma correlação quase significativa (P=0,008) entre as distâncias genéticas e morfométricas. A correlação observada não foi casual entre fenótipo e genótipo, mas indicou estruturas espaciais comuns. Desta forma, nossos resultados sugerem que processos de isolamento por distância poderiam explicar a divergência populacional na espécie Eupemphix nattereri.
RESUMO
To assess genetic structure and phenotypic diversity of Eupemphix nattereri Steindachner, 1863, morphometric and molecular analyses were carried out for nine populations from the State of Goiás. A total of 11 morphometric traits were evaluated and genetic information was estimated using RAPD markers. Genetic and phenotypic distances were determined as a function of geographical origin. Correlation among genetic, morphometric, micro, and macroenviromental were analyzed by the Mantel test. Genetic data indicated high levels of genetic diversity (st= 0.3) among the nine populations. Mantel tests did not reveal a significant positive correlation between genetic and geographical distances, indicating that locally geographical populations were not genetically similar, even in distances smaller than 50 km. Discriminant analysis on 11 morphometric measurements showed a high divergence among the nine populations. However, a marginally significant correlation (P=0.08) between genetic and morphometric distances was found. The observed correlation was not causal in terms of the relationship between phenotype and genotype, but indicated common spatial structures. Thus, our results suggest that isolation-by-distance processes may explain population divergence in Eupemphix nattereri.
Visando conhecer a estrutura genética e a diversidade fenotípica da espécie Eupemphix nattereri Steindachner, 1863, análises morfométricas e moleculares foram realizadas em nove populações do Estado de Goiás. Onze caracteres morfométricos foram avaliados e a diversidade genética foi estimada com o uso de marcadores RAPD. As matrizes de distâncias genéticas e fenotípicas foram correlacionadas com as distâncias geográficas e dados macro e microambientais, utilizando o teste de Mantel. Em relação aos caracteres genéticos, foram encontrados altos níveis de diversidade (st= 0,3) entre as nove populações. Não houve, entretanto, uma correlação positiva significativa entre as distâncias genéticas e geográficas, indicando que populações geograficamente próximas não seriam geneticamente similares, mesmo estando situadas entre distâncias menores do que 50 km. Uma análise discriminante dos onze caracteres morfométricos evidenciou também uma elevada divergência entre as nove populações. Entretanto, foi encontrada uma correlação quase significativa (P=0,008) entre as distâncias genéticas e morfométricas. A correlação observada não foi casual entre fenótipo e genótipo, mas indicou estruturas espaciais comuns. Desta forma, nossos resultados sugerem que processos de isolamento por distância poderiam explicar a divergência populacional na espécie Eupemphix nattereri.