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Clin Sci (Lond) ; 131(7): 583-594, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28143891

RESUMO

Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries. The mechanism of CAE remains unclear, and its treatment is limited. Previous studies have shown that risk factors for CAE were related to changes in DNA methylation. However, no systematic investigation of methylation profiles has been performed. Therefore, we compared methylation profiles between 12 CAE patients and 12 propensity-matched individuals with normal coronary arteries using microarrays. Wilcoxon's rank sum tests revealed 89 genes with significantly different methylation levels (P<0.05 and Δß > |0.1|). Functional characterization using the DAVID database and gene set enrichment analysis indicated that these genes were involved in immune and inflammatory responses. Of these genes 6 were validated in 29 CAE patients and 87 matched individuals with CAE, using pyro-sequencing. TLR6 and NOTCH4 showed significant differences in methylation between the two groups, and lower protein levels of toll-like receptor 6 (TLR6) were detected in CAE patients. In conclusion, this genome-wide analysis of methylation profiles in CAE patients showed that significant changes in both methylation and expression of TLR6 deserve further study to elucidate their roles in CAE.


Assuntos
Doença da Artéria Coronariana/genética , Vasos Coronários/patologia , Metilação de DNA , Adulto , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/imunologia , Dilatação Patológica/genética , Dilatação Patológica/imunologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/genética , Receptor Notch4 , Receptores Notch/genética , Receptor 6 Toll-Like/sangue , Receptor 6 Toll-Like/genética
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