Estudo da mutação PRO115GLN do gene PPAR[gama]2 e do polimorfismo G972R do gene IRS1 numa amostra populacional de individuos eutroficos e obesos

by Messaggi Gomes, Marcia Regina

Abstract (Summary)
Obesity is a complex, multifactorial disease that develops from the interaction between genotype and environment. It may be defined as a syndrome characterized by an increase in body fat storage and its prevalence has increased dramatically in industrialized and developing nations. There are several reasons for medical concern regarding overweight and obesity. It increases the risk for several diseases, especially cardiovascular diseases, type 2 Diabetes Mellitus and hypertension. The Peroxisome Proliferator-Activated Receptor (PPAR)-y is a transcription factor that belongs to the same family of nuclear receptors as steroid and thyroid hormone receptors. PP AR-y is a nuclear ligand-dependent transcription factor that promotes adipocyte differentiation and influences insulin sensitivity. A number of genetic variants in the PPARy gene have been identified. These include a very rare gain-of-function mutation (proI15Gln) that was associated by Ristow et al with obesity.The Insulin Receptor Substrate -1 (IRS-l) functions as a key proximal signaling molecule for both insulin receptor and insulin-like growth factor-l receptor signaling pathways. IRS-l is the principal substrate for insulin and insulin-like growth factor-l (IGF-1) receptors; it is present throughout tissues that are insulin sensitive, including sites responsible for glucose production, glucose clearance, and pancreatic j3-cells. A Gly~Arg substitution at codon 972 of IRS-l has been described as associated with obesity, particularly visceral obesity, with which insulin resistance is predominantly associated. The purpose of this study was to evaluate the presence of IRS-l G972R and PP ARy2 Pro 115Gln mutations in the Brazilian population. Sixty-seven lean and 64 obese/severely obese subjects (91women (32.9 i: 1.2 y) and 40 men (29.2 i: 1.7y) between 18 and 67 years of age) participated in the study. BM], waist circumference, fat mass (electrical bioimpedance), indirect calorimetry, blood pressure, fasting plasma glucose and insulin, serum uric acid, plasma lipids and HOMA-IR were evaluated. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction (PCR) and restriction enzyme digestion. Men presented larger waist circumference and larger waist-hip ratio than women (p=0.04 and p= 0.0001, respectively). Women presented larger fat percentage and lesser lean mass percentage in comparison with men (p< 0.0001). In relation to biochemical parameters, the female sex presented larger HDL-cholesterol values (p=0.03) and the male sex, a larger value for uric acid (pThis document abstract is also available in Portuguese.
Bibliographical Information:

Advisor:Laura Sterian Ward; Laura Sterian Ward [Orientador]; Mario Jose Abdalla Saad; Denise Giacomo da Motta

School:Universidade Estadual de Campinas

School Location:Brazil

Source Type:Master's Thesis



Date of Publication:08/25/2003

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