Assuntos
DNA Mitocondrial , Fígado Gorduroso/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , Estudos de Casos e Controles , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Fígado Gorduroso/etnologia , Fígado Gorduroso/fisiopatologia , Predisposição Genética para Doença , Humanos , Fígado/química , Hepatopatia Gordurosa não AlcoólicaRESUMO
We conducted a two-step case-control study to investigate the association between mtDNA variants and metabolic syndrome (MS) in Chinese. We initially screened 79 mitochondrial single nucleotide polymorphisms (mtSNPs) in 141 cases and 506 controls, and five mtSNPs had a p<0.05. We replicated results for the most significant mtSNP 10398A>G in additional 396 case and 424 controls (p=0.047, OR=1.26). The G allele frequency in the screening and follow up data was 66% and 55.2% in the cases, and 52.3% and 50.2% in the controls, respectively. Our results suggest the G allele of 10398A>G increases a risk for MS.
Assuntos
DNA Mitocondrial/genética , Predisposição Genética para Doença , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Somatic mitochondrial DNA alterations have been found in all types of cancer. To better understand the role of mitochondria and their involvement in the pathogenic mechanisms of cancer development, the effects of cancer mitochondria were investigated in a defined nuclear background using a transmitochondrial cybrid system. Our results demonstrated that cancer mitochondria confer a significant reduction in cell growth when cells are metabolically stressed in a galactose medium. Activities of the respiratory chain complexes, cellular oxygen consumption, and ATP synthesis rates were found to be much lower in breast cancer cells, than those in normal breast epithelial cells of MCF-10A (10A). These results suggest that there is reduced mitochondrial function in the studied breast cancer cell lines. Similarly reduced mitochondrial function was observed in cybrids containing cancer mitochondria. Novel tRNA mutations were also identified in two breast cancer cell lines, possibly responsible for the observed mitochondrial dysfunction. We conclude that altered mitochondria in cancer cells may play a crucial role in tumor development.