Associação entre variantes do gene da adiponectina (ADIPOQ): -11391 G/A, -11377 C/G, 45T>G e I164T e os níveis circulantes de adiponectina de alto peso molecular e fatores de risco cardiometabólico

• Autor(a) principal: Celoria, Bruno Miguel Jorge
• Data de Publicação: 2013
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12626
• topic: Obesity; Adiponectin; Polymorphism; Blood pressure; Obesidade; Adiponectina; Polimorfismo; Pressão arterial; Obesidade; Tecido adiposo; Resistência à insulina; Adiponectina; Síndrome X metabólica; Sistema cardiovascular; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::ENDOCRINOLOGIA

A diponectin, a hormone produced by adipose tissue, acts regulating energy metabolism and insulin sensitivity. Unlike other adipocytokines, adiponectin has an inverse association with visceral obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Recently, many studies have been demonstrating the effects of genetic variants in ADIPOQ gene on the circulating levels of adiponectin, blood pressure values, risk of non-alcoholic steatohepatitis and type 2 diabetes, and the emergence of obese phenotype. However, most of the results are controversial and have been related to studies conducted in Caucasian and Asian populations. The aim of the present study was to evaluate, in a multiethnic adult population of the metropolitan region of Rio de Janeiro, the possible effects of the genetic variants (-11391 G>A, -11377C>G, +45T>G e T517G) in ADIPOQ gene on the obese phenotype, circulating levels of adiponectin and high sensitivity and quantitative C-reactive protein, and cardiometabolic risk factors. We evaluated 100 lean individuals (BMI 18,5 24,9 kg/m2, age: 32,5 + 9,8 years) and 100 obese individuals (BMI 30 58,2 kg/m2, age 37,5 + 14,1 years), equally distributed men and women. The obese subjects showed high levels of abdominal circunference, blood pressure, fasting glucose, triglycerides, LDL-cholesterol, leptin, insulin, HOMA-IR and C-reactive protein, and exhibited lower levels of HDL-cholesterol and adiponectin, when compared to euthrophic individuals. Correlation analysis showed an inverse relationship between adiponectin and abdominal circumference, insulin, HOMA-IR and blood pressure, and a positive correlation with HDL-cholesterol. Stepwise regression analysis revealed that gender, abdominal circumference, HOMA-IR and the -11391G>A polymorphism were independently related with adiponectin levels. Regarding to the molecular analyses, no association was found between these variants and the obese phenotype. However, the subjects carrying the -11391G>A polymorphism showed lower values of waist to hip ratio, glucose and blood pressure, and higher levels of adiponectin, when compared to wild subjects. Furthermore, the subjects carrying the -11377 C>G polymorphism demonstrated lower levels of systolic, diastolic and mean blood pressure. The results of our study have shown that adiponectin levels differ between lean and obese individuals and that lower levels of this adipocytokine are associated with a worse cardiometabolic profile. Genetic variants in ADIPOQ gene may interfere in this relationship. We conclude that the polymorphisms -11391G>A and -11377 C>G may predict outcome of cardiovascular risk.