RESUMO
The prevalence of childhood obesity has increased worldwide. Although it is considered a polygenic inheritance disease, little is known about its susceptibility when the additive effect is considered. The aim of this study is to investigate whether the genetic risk score (GRS) based on previously associated obesity polymorphisms (SNP) rs9939609 (fat mass and obesity-associated (FTO)), rs6548238 (transmembrane protein 18 (TMEM18)) and rs16835198 (fibronectin type III domain containing 5 (FNDC5)) could serve as a predictor for anthropometric characteristics in a sample of Brazilian children and adolescents. This is a cross-sectional study with 1471 children and adolescents aged 6-17 years. BMI, waist circumference (WC) and percentage of body fat and metabolic parameters were verified. In all, three SNP were genotyped by TaqMan™ allelic discrimination. The metabolic and anthropometric parameters were compared between the genotypes, and the unweighted and weighted GRS (GRS and wGRS, respectively) were created to test the additive effect of these genetic polymorphisms on anthropometric parameters. The prevalence of overweight plus obesity was 41 %. Significant associations were identified for FTO rs9939609, TMEM18 rs6548238 and FNDC5 rs16835198 and for GRS and wGRS with anthropometric phenotypes. The higher score of wGRS was associated with obesity (OR: 2·65, 95 % CI 1·40, 5·04, P=0·003) and with greater WC (OR: 2·91, 95 % CI 1·57, 5·40, P=0·001). Our results suggest that these genetic variants contribute to obesity susceptibility in children and adolescents and reinforce the idea that the additive effect may be useful to elucidate the genetic component of obesity.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Fibronectinas/genética , Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Obesidade Infantil/genética , Adolescente , Antropometria , Composição Corporal/genética , Índice de Massa Corporal , Brasil/epidemiologia , Criança , Feminino , Genótipo , Humanos , Masculino , Obesidade Infantil/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Circunferência da Cintura/genéticaRESUMO
Activation of adipose tissue inflammation is associated with obesity caused by lipid accumulation in adipocytes. Through this activation, proinflammatory cytokines, such as Interleukin-6 (IL-6) and C-reactive protein (CRP) seem to influence metabolic disorders. The present study evaluated whether polymorphisms in the CRP (rs1205) and IL-6 (rs1800795, rs2069845) genes are associated with the development of metabolic disorders in children and adolescents. A cross-sectional study was performed, consisting of 470 students from the municipality of Santa Cruz do Sul, Brazil, aged 7-17 years. Body mass index (BMI) was classified according to overweight and obesity. Genotyping was performed by real-time Polymerase Chain Reaction (PCR). Anthropometric characteristics, biochemical markers, immunological markers and blood pressure were assessed. Descriptive statistics, chi-square and logistic regression were used for the analyses. No association was detected between the rs1800795 polymorphism and the assessed variables. Individuals with the risk genotype in the rs1205 gene were associated with the risk of developing hypercholesterolemia (OR 2.79; CI 1.40, 5.57; p = 0.003). Carriers of the risk genotype in the rs2069845 gene are associated with the risk of developing obesity (OR 3.07; CI 1.08, 8.72; p = 0.03). The polymorphism rs2069845 was associated with obesity and rs1205 was associated with the risk of developing hypercholesterolemia in Brazilian schoolchildren.
Assuntos
Proteína C-Reativa/genética , Interleucina-6/genética , Obesidade/genética , Polimorfismo Genético , Adolescente , Biomarcadores/metabolismo , Índice de Massa Corporal , Brasil , Proteína C-Reativa/metabolismo , Criança , Estudos Transversais , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-6/metabolismo , Masculino , Obesidade/metabolismo , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
Anti-tuberculosis drug-induced hepatitis (ATD- induced hepatitis) has been linked to polymorphisms in genes encoding drug metabolizing enzymes. N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1) and glutathione S-transferase (loci GSTM1 and GSTT1) are involved in the metabolism of isoniazid, the most toxic drug for the treatment of tuberculosis (TB). This study was designed to determine the frequency and to evaluate whether polymorphisms at CYP2E1, GSTM1 and GSTT1 genes are associated with drug response, as well as to identify clinical risk factors for ATD-induced hepatitis. A total of 245 Brazilian patients undergoing treatment for TB were genotyped using polymerase chain reaction and restriction fragment length polymorphism and sequencing methods. The frequencies of the CYP2E1 polymorphic alleles RsaI, PstI and DraI are 8%, 8.5% and 12%, respectively. GSTM1 and GSTT1 genes are deleted in 42.9% and 12.4% of the population, respectively. Fifteen patients (6.1%) developed hepatotoxicity. Clinical (HIV, female sex and extrapulmonary TB) and genetic characteristics (CYP2E1 without any mutations, having NAT2 slow acetylator profile) are at higher risk of developing ATD-induced hepatitis in this population. Genotyping for GSTM1 and GSTT1 showed no influence on drug response.