ABSTRACT
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.
Subject(s)
Coronary Artery Disease/genetics , Coronary Vessels/pathology , DNA Methylation , Adult , Aged , Case-Control Studies , Coronary Artery Disease/immunology , Dilatation, Pathologic/genetics , Dilatation, Pathologic/immunology , Female , Genetic Predisposition to Disease , Genome-Wide Association Study/methods , Humans , Inflammation/genetics , Male , Middle Aged , Proto-Oncogene Proteins/genetics , Receptor, Notch4 , Receptors, Notch/genetics , Toll-Like Receptor 6/blood , Toll-Like Receptor 6/geneticsABSTRACT
The aim of the present study was to investigate the epidemiology of Legionnaires' disease (LD) caused by Legionella longbeachae in Taiwan during 2006-2010. A total of six cases were identified prospectively, accounting for 1.6% of all laboratory-confirmed LD cases and 4.4% of culture-positive LD cases. All six cases occurred between April and August. The male to female ratio was 0.5. These six LD patients had a higher median age than those with LD due to Legionella pneumophila. Four of the six patients presented with pleural effusion and five survived the infection episode. Only two patients had a potential soil contact history prior to LD onset. The patients resided in divergent geographical areas without a common exposure history. The individual genomic DNA banding patterns of the six L. longbeachae isolates analyzed by pulsed-field gel electrophoresis (PFGE) were unique, supporting the hypothesis that the L. longbeachae infections occurred sporadically.
