Polymorphisms in Genes Tcf7l2 and Adipoq and Its Association With
Obesity and Diabetes in Teens of Greater Vitória
Name: JOSIVANY VALÉRIO DE FREITAS COSTA
Type: PhD thesis
Publication date: 30/08/2016
Advisor:
Name |
Role |
|---|---|
| FLAVIA DE PAULA (M/D) | Advisor * |
| FLAVIA IMBROISI VALLE ERRERA | Co-advisor * |
Examining board:
| Name |
Role |
|---|---|
| FLAVIA DE PAULA (M/D) | Advisor * |
| FLAVIA IMBROISI VALLE ERRERA | Co advisor * |
| MARIA DO CARMO PIMENTEL BATITUCCI | External Examiner * |
| SANDRA LÚCIA VENTORIN VON ZEIDLER | Internal Examiner * |
Summary: Obesity is a chronic disease characterized by excess fat and has increased significantly among children and adolescents leading to various complications in childhood and adulthood, such as hypertension, intolerance diminuiada glucose, dyslipidemia and type 2 diabetes (T2D). A number of factors contribute to obesity in childhood and can be:
genetic, environmental and behavioral. Studies have investigated the genetic factors that predispose to obesity, although these factors are still poorly understood. The candidate genes predisposing to obesity are related to the regulation of hunger, energy balance, glucose and lipid metabolism; and differentiation of adipocytes. In this context,
polymorphism analysis of factor transcription gene 7 like-2 (TCF7L2) encoding a transcription factor involved in signaling Wnt catenin-dependent pathway important for growth functions, metabolism and cell survival, and ADIPOQ gene regulating insulin sensitivity, and is involved in inflammatory response, and regulation of energy balance, represent an interesting opportunity to identify the primary genetic determinants involved in susceptibility to obesity and type 2 diabetes in children, since they are a major target groups for research strategies, prevention and control of overweight and obesity. This study aimed to analyze the frequencies of genotypes for rs7903146 polymorphism TCF7L2 gene and rs2241766 polymorphisms (+ 45T> G) and rs1501299 (+276 G> T) in ADIPOQ gene in adolescents and check whether any genotype and / or model gene is
associated to the presence of obesity and / or diabetes type 2. adolescents enrolled in public schools in the Metropolitan Region of Vitória-ES, from a representative sample of the study "Prevalence of overweight and obesity in adolescents in the state of Espirito Santo and his association with some variables of the metabolic syndrome "were
randomly included in the genetic study. The anthropometric measurements and blood collection, after fasting for 12 hours, were held at the school. For the nutritional status was considered the body mass index / age (BMI / A), z score. Genomic DNA was extracted from peripheral blood samples. For TCF7L2 gene DNA was amplified by chain reaction allele-specific polymerase and the products of this reaction were analyzed by
polyacrylamide gel electrophoresis (12%), visualized by staining with silver nitrate 0.1%. For ADIPOQ gene DNA was amplified by Taqman methodology. Statistical analysis was performed using SPSS software version 23.0. Data of individuals relating to race, gender, age, BMI / A, glucose and HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) were analyzed. For TCF7L2 gene was investigated 326 adolescents (age: 10-14 years) divided into without obesity group (n = 299) and obesity (n = 27). We also analyzed the frequencies for dominant genetic models (TT + CT x CC), recession (CC + CT x TT) and additive (TT x CC), but only to the dominant model was verified a marginal association (P = 0.054). As the age differed between groups (P = 0.011), the sample was stratified into two subgroups: ≤12 years and> 12 years. The dominant genetic model (TC + CC TT X) for the polymorphism rs7903146, with HOMA-IR and age
explained obesity in adolescents. The other parameters analyzed in both groups, were not associated with any genotype or genetic model. There was no association between the polymorphism rs 7903146 and early changes of glucose metabolism, but the increased risk of obesity in the first phase of adolescence. For ADIPOQ gene were investigated 355 adolescents aged 10-14 years, who were divided into two groups: overweight (n = 110) and without overweight (n = 245). For the single nucleotide polymorphism (SNP) 45 T> G genotypes observed association of overweight (p = 0.04)
and dominant genetic templates for the T allele and additive with overweight (p = 0.03), this SNP was also associated with increased BMI / A. For SNP 276 G> T no association of genotypes with excess weight and the GT genotype (p = 0.02) and the dominant genetic model template for the T allele (p = 0.02) in this SNP were associated with higher fasting glucose levels in adolescents in this study. We conclude that the 45 SNPs T> G and 276 G> T are respectively associated with increased BMI/A and fasting glycemia in adolescents in the age group between 10 - 14 years.
