title: Genome-wide methylation profiles in coronary artery ectasia.
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 Δβ > |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.TLR6andNOTCH4showed 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 ofTLR6deserve further study to elucidate their roles in CAE.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, Department of Public Health, National Taiwan University, Taiwan.
authors.forename: Tzu-Pin
authors.initials: TP
authors.lastname: Lu
authors.affiliation: Institute of Epidemiology and Preventive Medicine, Department of Public Health, National Taiwan University, Taiwan.
authors.forename: Nai-Chen
authors.initials: NC
authors.lastname: Chuang
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan.
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan.
authors.forename: Cheng-An
authors.initials: CA
authors.lastname: Hsu
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Yen-Hong
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Jen-Kuang
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Cho-Kai
authors.initials: CK
authors.lastname: Wu
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Juey-Jen
authors.initials: JJ
authors.lastname: Hwang
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors.forename: Lian-Yu
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Department of Medical Education, National Taiwan University Hospital and National Taiwan University College of Medicine, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taiwan.
authors.forename: Shih-Fan Sherri
authors.initials: SS
authors.lastname: Yeh
authors.affiliation: Institute of Epidemiology and Preventive Medicine, Department of Public Health, National Taiwan University, Taiwan.
authors.forename: Kuo-Liang
authors.initials: KL
authors.lastname: Chien
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan p91421019@ntu.edu.tw.
authors.forename: Jyh-Ming Jimmy
authors.initials: JJ
authors.lastname: Juang
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000276:immunology; D003331:Coronary Vessels / Q000473:pathology*; D019175:DNA Methylation; D004108:Dilatation, Pathologic / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics; D051216:Toll-Like Receptor 6 / Q000097:blood / Q000235:genetics
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch; C495368:TLR6 protein, human; D051216:Toll-Like Receptor 6
keywords: TLR6; coronary artery ectasia; methylation; microarray