title: Integration of gene expression and DNA methylation profiles provides a molecular subtype for risk assessment in atherosclerosis.
abstract: The aim of the present study was to identify an effective method for detecting early‑phase atherosclerosis (AS), as well as to provide useful DNA methylation profiles to serve as biomarkers for the detection of AS. A total of 300 individuals (150 AS patients and 150 healthy subjects) were recruited for peripheral blood DNA methylation analyses at 12 gene promoter loci using nested methylation‑speciﬁc polymerase chain reaction in a test set. Based on the test set, the promoter methylation of TIMP metallopeptidase inhibitor 1 (TIMP1), ATP binding cassette subfamily A member 1 (ABCA1), and acetyl-CoA acetyltransferase 1 (ACAT1) were determined to be candidate biomarkers; demonstrating the highest sensitivity (88%) and specificity (90%). The biomarkers that were candidates for early AS detection were validated in an independent validation set (n=100). In the validation set, the combination of TIMP1, ABCA1 and ACAT1 methylation achieved sensitivity, specificity and coincidence rate values of 88, 70 and 79%, respectively. In the current pilot study, the patterns of DNA methylation of AS‑associated genes were observed to be significantly altered in the peripheral blood of AS patients. Thus, the AS-specific methylation of the three‑gene panel (TIMP1, ABCA1, and ACAT1) may serve as a valuable biomarker for the early detection of AS.
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Sheng-Chao
authors.initials: SC
authors.lastname: Ma
authors.affiliation: Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Fan-Qi
authors.initials: FQ
authors.lastname: Kong
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: He
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: An-Ning
authors.initials: AN
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Ming-Hao
authors.initials: MH
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
authors.forename: Yi-Deng
authors.initials: YD
authors.lastname: Jiang
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics; D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D042241:Early Diagnosis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D014408:Biomarkers, Tumor; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D004247:DNA; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase