Estudo de polimorfismo do gene que codifica a enzima óxido nítrico sintase (eNOS) e relações de ancestralidade de pacientes com insuficiência cardíaca

• Autor(a) principal: Oliveira, Romulo Vianna de Melo
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/16318
• topic: Heart failure; Genetic markers; Endothelial nitric oxide synthase; Ancestry; Insuficiência cardíaca; Marcadores genéticos; Óxido nítrico sintase endotelial; Ancestralidade; Insuficiência cardíaca; Polimorfismo genético; Hereditariedade; Óxido nítrico; Marcadores genéticos; Grupo com ancestrais do continente africano; Grupo com ancestrais do continente europeu; CNPQ::CIENCIAS BIOLOGICAS::GENETICA

The heart failure (HF) is a complex syndrome characterized by an impairment of the left ventricle that causes a lower blood ejection to the blood vessels. Even with the therapeutic improvements, the HF is still one of the main causes of mortality, hospitalization, and functional limitation in Brazil and worldwide. Some studies suggest an association between the G894T polymorphism, located in the gene responsible for encoding endothelial nitric oxide synthase enzyme (eNOS) and HF prognosis in certain populations. However, the allelic and genotypic frequencies for the G894T polymorphism are very different according to the studied populations, and the association between G894T and HF was only found in well-defined populations such as European and African-American. Therefore, it is justified the investigation in a admixed population as Brazilian, using ancestry informative markers (AIMs) as a tool in each individual of the study in order to reduce the effects of population stratification, a recurrent problem in studies involving the Brazilian population, avoiding spurious association. The objectives of this study were to determine the allelic and genotypic frequency distributions for the G894T polymorphism, located inside the eNOS gene, in samples of patients and healthy individuals, considering the ancestral profiles, and to investigate an association between the polymorphism and the HF. The study included 210 individuals from the study cohort involving patients with HF from the Hospital Universitário Pedro Ernesto/UERJ and 106 healthy individuals. The DNA sequence including the G894T polymorphism from the eNOS gene was amplified by PCR and genotyped by restriction analysis. The ancestry information was obtained from 46 AIMs autosomal markers, genotyped by PCR followed by capillary electrophoresis. Concerning the ancestry profile, both the patients and controls showed a major European contribution, followed by African and Native American, without a significant difference between the two groups. The frequencies of the wild homozygous (GG) and the variant allele (T) were higher in HF patients than in healthy individuals. These differences showed a statistical significance with an associative odds ratio value for increased chance for IC prognosis in subjects with GG genotype and a reduced chance for individuals with T allele. The frequencies of the homozygous genotypes (GG and TT) were higher in patients with a non-severe case of HF than in those with severe forms, a difference that was statistically significant and indicates a higher incidence of severe cases on subjects with GT genotype. This study suggests an association of GG genotype with a higher incidence of HF and a lower incidence in subjects with T allele.