Polimorfismos gênicos e danos no DNA em indivíduos com obesidade mórbida
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Data
2012-02-27
Autores
Luperini, Bruno Cesar Ottoboni [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A obesidade é uma desordem multifatorial que envolve fatores hereditários, ambiente e estilo de vida, e suas consequências não são apenas sociais ou psicológicas, mas estão também relacionadas à presença de co-morbidades como a hipertensão arterial, diabetes tipo 2, doenças cardiovasculares e vários tipos de câncer. Sabe-se, hoje, que há genes relacionados ao peso corporal, embora as relações entre genética e obesidade sejam ainda questões de muito debate. Portanto, o presente estudo teve como objetivos avaliar os níveis de danos no DNA (teste cometa) em linfócitos de pacientes obesas (n=300) e mulheres eutróficas (n=300); a frequência de polimorfismos dos genes FTO (rs9939609) e APM1: 45T/G (rs2241766) e a existência de associação entre essas variantes gênicas e a incidência de lesões genotóxicas nessas populações. Os dados obtidos evidenciaram que as mulheres obesas possuem maiores níveis de lesões primárias no DNA de linfócitos, incluindo purinas e pirimidinas oxidadas, independentemente de seus genótipos para os genes FTO e APM1. A avaliação das variantes do gene FTO mostrou que os genótipos AA e TT foram, respectivamente, mais e menos frequentes nas pacientes obesas do que nas mulheres do grupo controle e que aquelas com a variante AA em ambos os grupos apresentaram maiores níveis de lesões nos DNA. Para o gene APM1, o genótipo TT foi o mais frequente em ambos os grupos, mas as mulheres com as variantes TG+GG foram as que apresentaram níveis mais elevados de lesões genotóxicas. Esses resultados indicaram, portanto, que a obesidade está relacionada a níveis mais altos de lesões genotóxicas em linfócitos de sangue periférico e que o genótipo AA do gene FTO, além de ser mais frequente em mulheres com obesidade mórbida está associado a maiores níveis de danos no DNA, assim como o alelo G do gene APM1. Assim sendo, pode-se...
Obesity is a multifactorial disorder which involves heredity, environment and lifestyle. Its consequences are not just social or psychological, but also related to the presence of comorbidities such as hypertension, type 2 diabetes, cardiovascular disease and various types of cancer. Although some genes have been associated to body weight, the relationship between genetics and obesity are still object of debate. Therefore, this study aimed to assess the level of DNA damage (comet assay) in lymphocytes from morbid obese patients (n=300) and normal weight women (n=300); the frequencies of FTO (rs9939609) and APM1: 45T/G (rs2241766) gene polymorphisms and the relationship between these gene variants and the amount of genotoxic damage were also investigated. Data showed higher level of DNA primary lesions, including oxidized purines and pyrimidines, in lymphocytes of obese than in eutrophic women, regardless their FTO and APM1 genotypes. The AA and TT FTO genotypes were respectively more and less frequents in obese patients than in the control population. Those women with the AA variant, in both groups, presented the highest levels of DNA damage. For APM1 gene, TT genotype was the most frequent in both groups, however women with the allele G (TG+GG variants) presented the highest levels of genotoxic damage. These results indicated that obesity is associated to high levels of genotoxic damage in peripheral blood lymphocytes, and that the AA genotype of the FTO gene is related to morbid obesity and to the highest levels of DNA damage, as well as the G allele of the APM1 gene. In conclusion, obese patients with FTO AA genotypes are at higher risk... (Complete abstract, click access below)
Obesity is a multifactorial disorder which involves heredity, environment and lifestyle. Its consequences are not just social or psychological, but also related to the presence of comorbidities such as hypertension, type 2 diabetes, cardiovascular disease and various types of cancer. Although some genes have been associated to body weight, the relationship between genetics and obesity are still object of debate. Therefore, this study aimed to assess the level of DNA damage (comet assay) in lymphocytes from morbid obese patients (n=300) and normal weight women (n=300); the frequencies of FTO (rs9939609) and APM1: 45T/G (rs2241766) gene polymorphisms and the relationship between these gene variants and the amount of genotoxic damage were also investigated. Data showed higher level of DNA primary lesions, including oxidized purines and pyrimidines, in lymphocytes of obese than in eutrophic women, regardless their FTO and APM1 genotypes. The AA and TT FTO genotypes were respectively more and less frequents in obese patients than in the control population. Those women with the AA variant, in both groups, presented the highest levels of DNA damage. For APM1 gene, TT genotype was the most frequent in both groups, however women with the allele G (TG+GG variants) presented the highest levels of genotoxic damage. These results indicated that obesity is associated to high levels of genotoxic damage in peripheral blood lymphocytes, and that the AA genotype of the FTO gene is related to morbid obesity and to the highest levels of DNA damage, as well as the G allele of the APM1 gene. In conclusion, obese patients with FTO AA genotypes are at higher risk... (Complete abstract, click access below)
Descrição
Palavras-chave
Polimorfismo (Genetica), DNA, Obesidade mórbida, Morbid obesity
Como citar
LUPERINI, Bruno Cesar Ottoboni. Polimorfismos gênicos e danos no DNA em indivíduos com obesidade mórbida. 2012. 69 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2012.