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Master's Dissertation
DOI
https://doi.org/10.11606/D.9.2014.tde-26052015-143307
Document
Author
Full name
Aécio Assunção Braga
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Hirata, Mario Hiroyuki (President)
Hirabara, Sandro Massao
Passarelli, Marisa
Title in Portuguese
Polimorfismos dos genes CD40, ICAM-1, VCAM, E-selectina, LIGHT, RAGE e CX3CR1 relacionados com inflamação e sua associação à obesidade
Keywords in Portuguese
Citocinas
Expressão gênica
Inflamação
Obesidade
Polimorfismos
Abstract in Portuguese
INTRODUÇÃO: A obesidade é um grave problema de saúde pública, sendo definida como o acúmulo excessivo de gordura, possivelmente decorrente do desequilíbrio, por um longo período, entre a quantidade de energia ingerida e o gasto energético. OBJETIVO: Investigar a contribuição dos polimorfismos dos genes CD40, ICAM-1, VCAM, E-selectina, LIGHT, RAGE e CX3CR1 na associação com a obesidade. CASUÍSTICA E MÉTODOS: O estudo foi realizado no Instituto Dante Pazzanese de Cardiologia (IDPC) e no Hospital Universitário da Universidade de São Paulo (HU/USP), com 199 indivíduos (40 com peso normal, 55 com sobrepeso e 104 obesos) brasileiros, sem vínculo genético, de etnias branca, parda, negra e amarela, de ambos os sexos (55 homens e 144 mulheres), com idade entre 30 e 68 anos. Foi realizado o estudo dos polimorfismos dos genes CD40 (rs1883832) C>T, CX3CR1 (rs3732379) C>T, CX3CR1 (rs3732378) G>A, E-selectina (rs5368) C>T, ICAM-1 (rs1799969) G>A, ICAM-1 (rs281432) C>G, LIGHT (rs344560) G>A, LIGHT (rs2291668) C>T, RAGE (rs2070600) G>A, RAGE (rs2236493) C>T e VCAM (rs3176878) C>T, por pirossequenciamento, a análise da expressão dos genes LIGHT, CX3CR1, RAGE e ICAM-1, pela PCR em tempo real, e as dosagens das formas solúveis de PAI-1, IL-6, TNF-α, resistina, adiponectina e leptina, utilizando o sistema LUMINEX. RESULTADOS: As frequências alélica e genotípica dos polimorfismos estudados CD40 (rs1883832) C>T, CX3CR1 (rs3732379) C>T, CX3CR1 (rs3732378) G>A, E-selectina (rs5368) C>T, ICAM-1 (rs1799969) G>A, ICAM-1 (rs281432) C>G, LIGHT (rs344560) G>A, LIGHT (rs2291668) C>T, RAGE (rs2070600) G>A, RAGE (rs2236493) C>T e VCAM (rs3176878) C>T não apresentaram associação significativa com a obesidade. Foi encontrada associação na análise da expressão do CX3CR1 com a obesidade e também foi encontrada associação do polimorfismo ICAM-1 (rs281432) G>C com a expressão do gene RAGE em indivíduos com peso normal. CONCLUSÕES: Não houve associação dos polimorfismos CD40 (rs1883832) C>T, CX3CR1 (rs3732379) C>T, CX3CR1 (rs3732378) G>A, E-selectina (rs5368) C>T, ICAM-1 (rs1799969) G>A, ICAM-1 (rs281432) C>G, LIGHT (rs344560) G>A, LIGHT (rs2291668) C>T, RAGE (rs2070600) G>A, RAGE (rs2236493) C>T e VCAM (rs3176878) C>T com a obesidade, mas houve associação da expressão do gene CX3CR1 com a obesidade. Houve, também, associação do polimorfismo ICAM-1 (rs281432) G>C com a expressão do gene RAGE em indivíduos de peso normal.
Title in English
Polymorphisms of CD40, ICAM-1, VCAM, E-selectin, LIGHT, RAGE and CX3CR1 polymorphisms genes related to inflammation and its association with obesity
Keywords in English
Cytokines
Gene expression
Inflammation
Obesity
Polymorphisms
Abstract in English
Background: Obesity is a serious health problem and it is defined as an excessive fat accumulation which is caused by an imbalance between the amount of energy intake and energy expenditure over a long period. Objective: The main objective of this study was to investigate the contribution of CD403 ICAM-1, VCAM, E-selectin, LIGHT, RAGE e CX3CR1 gene polymorphisms and its association with obesity. Material and Methods: The study was realized at Dante Pazzanese Institute of Cardiology and University Hospital of São Paulo University. There were included 199 individuals (40 normal weight, 55 overweight and 104 obese), all Brazilian, with no genetic link, from all ethnics in both genders (55 men and 144 women), aged between 30 and 68 years. The study of CD40 (rs1883832) C>T, CX3CR1 (rs3732379) C>T, CX3CR1 (rs3732378) G>A, E-selectin (rs5368) C>T, ICAM-1 (rs1799969) G>A , ICAM-1 (rs281432) C>G, LIGHT (rs344560) G>A, LIGHT (rs2291668) C>T, RAGE (rs2070600) G>A, RAGE (rs2236493) C>T and VCAM (rs3176878) C>T were conducted by pyrosequencing. The analysis of LIGHT, CX3CR1, RAGE and ICAM-1 gene expression were performed by real-time PCR and the measurements of PAI-1, IL- 6, TNF-a, resistin, leptin and adiponectin soluble forms using LUMINEX system. Results: The allele and genotype frequency of CD40 (rs1883832) C>T, CX3CR1 (rs3732379) C>T, CX3CR1 (rs3732378) G>A, E-selectin (rs5368) C>T, ICAM-1 (rs1799969) G>A , ICAM-1 (rs281432) C>G, LIGHT (rs344560) G>A, LIGHT (rs2291668) C>T, RAGE (rs2070600) G>A, RAGE (rs2236493) C>T and VCAM (rs3176878) C>T gene polymorphisms showed no significant association with obesity. There was found association in the analysis of CX3CR1 expression with obesity and it was found association of ICAM-1 gene polymorphism (rs281432) G>C with RAGE gene expression in the normal weight group. Conclusion: There was no association of CD40 (rs1883832) C>T, CX3CR1 (rs3732379) C>T, CX3CR1 (rs3732378) G>A, E-selectin (rs5368) C>T, ICAM-1 (rs1799969) G>A , ICAM-1 (rs281432) C>G, LIGHT (rs344560) G>A, LIGHT (rs2291668) C>T, RAGE (rs2070600) G>A, RAGE (rs2236493) C>T and VCAM (rs3176878) C>T gene polymorphisms with obesity. However, it was found association of CX3CR1 gene expression with obesity and an association of ICAM-1 (rs281432) G>C gene polymorphism with RAGE gene expression in normal weight individuals.
 
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Publishing Date
2015-07-20
 
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