RESUMO
Introduction. Increase in body weight is a gradual process that usually begins in childhood and in adolescence as a result of multiple interactions among environmental and genetic factors. This study aimed to analyze the relationship between copy number variants (CNVs) in five genes and four intergenic regions with obesity in Mexican children. Methods. We studied 1423 children aged 6-12 years. Anthropometric measurements and blood levels of biochemical parameters were obtained. Identification of CNVs was performed by real-time PCR. The effect of CNVs on obesity or body composition was assessed using regression models adjusted for age, gender, and family history of obesity. Results. Gains in copy numbers of LEPR and NEGR1 were associated with decreased body mass index (BMI), waist circumference (WC), and risk of abdominal obesity, whereas gain in ARHGEF4 and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d and losses in INS were associated with increased BMI and WC. Conclusion. Our results indicate a possible contribution of CNVs in LEPR, NEGR1, ARHGEF4, and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d to the development of obesity, particularly abdominal obesity in Mexican children.
Assuntos
Moléculas de Adesão Celular Neuronais/genética , Proteínas de Ligação a DNA/genética , Obesidade Abdominal/genética , Receptores para Leptina/genética , Composição Corporal/genética , Índice de Massa Corporal , Peso Corporal/genética , Criança , Variações do Número de Cópias de DNA/genética , DNA Intergênico/genética , Feminino , Proteínas Ligadas por GPI/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , México , Obesidade Abdominal/fisiopatologia , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Circunferência da Cintura/genéticaRESUMO
Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.
Assuntos
Proteínas de Transferência de Ésteres de Colesterol/genética , Receptor alfa de Estrogênio/genética , Haplótipos , Lipase Lipoproteica/genética , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Desequilíbrio de Ligação , México/epidemiologia , Pessoa de Meia-IdadeRESUMO
Type 2 diabetes (T2D) is a disease characterized by a deficiency in production or action of insulin. It is the result mainly of the interaction of the environment, lifestyle, as well as genetic factors. It is considered as one of the major health issues in the world because it affects severely the psychological well-being and overall life quality. Recently it has been shown that DNA copy number variations (CNVs) are associated with several diseases, including obesity and T2D. The CNVs are present from 9 to 18 % of the genome and can modify the expression levels of mRNA and proteins encoded by genes located near their localization. Less is known about their contribution to the pathogenesis of metabolic diseases, which is necessary to characterize so that these variations can be potentially used as biomarkers of genetic risk CNVs of T2D.
La diabetes tipo 2 (DT2) es una enfermedad caracterizada por una deficiencia en la producción o acción de la insulina; es el resultado de la interacción principalmente de factores ambientales, el estilo de vida, asícomo factores genéticos. Se considera como uno de los problemas de salud más importantes en el mundo debido a que afecta seriamente la independencia, el bienestar psicológico y en general la calidad de vida. Recientemente se ha demostrado que las variaciones en el número de copias de ADN (CNV, del inglés copy number variations) se asocian con diferentes enfermedades, entre ellas la obesidad y DT2. Las CNV se presentan en el 9 al 18 % del genoma y pueden modificar los niveles de expresión de mRNA y proteína codificados por genes cercanos a su ubicación. Poco se conoce acerca de su contribución en la patogénesis de las enfermedades metabólicas, por lo cual es necesario caracterizar estas variaciones para que potencialmente sean utilizadas como biomarcadores genéticos de riesgo de DT2.
