ABSTRACT
Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. The adrenergic receptor ¦Â3 (¦Â3-AR), leptin (LEP) and leptin receptor (LEPR) genes have been intensively evaluated in the search of variants that could be related to obesity and its cardiometabolic complications. The results of most of these studies have been controversial. In the present study, we investigated the relationship of the ¦Â3-AR p.W64R, LEP c.-2548G>A and LEPR p.Q223R gene variants with body mass index (BMI), in Brazilian subjects of different genetic backgrounds and ethnic origins. Two hundred obese patients (60 males, 140 females, BMI ¡Ý 30 kg/m2) were screened and compared to 150 lean healthy subjects (63 males, 87 females, BMI ¡Ü 24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction. Polymerase chain reaction products were digested with specific restriction enzymes and separated by electrophoresis. There was no significant difference in the genotype frequency of the ¦Â3-AR p.W64R and the LEP c.-2548G>A polymorphisms, between lean and obese subjects. However, the genotype and allele frequencies of the LEPR p.Q223R variant were significantly different between the normal weight and obese groups. Haplotype analysis has shown an association between the G/G allelic combination of c.-2548G>A LEP and c.668A>G LEPR, in obese subjects. Our results suggest that genetic variability in the leptin receptor is associated with body weight regulation, the LEPR p.Q223R variant being related to BMI increase. The haplotype combination of LEP c.-2548G>A and LEPR p.Q223R variants was related to a 58% increase in obesity risk.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Genetic Variation , Obesity/genetics , /genetics , Alleles , Body Mass Index , Brazil , Case-Control Studies , DNA , Gene Frequency , Obesity/pathology , Polymorphism, Single Nucleotide , Amino Acid Substitution/geneticsABSTRACT
Neste estudo investigamos a organizaçäo cromossômica de pacientes com retardo mental e/ou malformaçöes congênitas, visando a avaliaçäo de causas genéticas associadas a estes distúrbios. Os padröes de bandas GTG e CBG foram estudados a partir da cultura de linfócitos de sangue periférico, estimulados por fitohemaglutinina M. Dentre os 98 indivíduos portadores de retardo mental e/ou malformaçöes congênitas analisados, diagnosticamos as seguintes síndromes: 12 casos de Down, dois de Edwards, um de Patau, cinco de Turner, dois de Klinefelter, um de "cri-du-chat", e um caso de translocaçäo balanceada entre os cromossomos 13 e 14, um caso de cromossomo derivado e um outro de cromossomo marcador. Encontramos anomalias cromossômicas em 26 por cento dos pacientes, das quais 82 por cento eram alteraçöes numéricas e o restante (18 por cento) representou rearranjos estruturais. Este percentual significativo enfatiza o uso da cariotipagem de rotina em pacientes com retardo mental e/ou malformaçöes congênitas.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Chromosome Aberrations , Genetic Counseling , Intellectual Disability , KaryotypingABSTRACT
O retardo mental é uma característica comum aos pacientes que buscam o Serviço de Genética Médica, apresentando heterogeneidade clínica e etiológica. Neste trabalho, estudos cromossômicos foram realizados em 30 indivíduos portadores de retardo mental e atraso psicomotor. Verificamos que 40 por cento dos indivíduos investigados apresentaram anomalias cromossômicas. Nos demais casos (60 por cento) o cariótipo foi normal. Este estudo reforça a importância da investigaçåo citogenética em indivíduos portadores de retardo mental e atraso psicomotor rastreando aberraçöes cromosssômicas numéricas ou estruturais e auxiliando no diagnóstico, prognóstico e aconselhamento gewnético das famílias