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DNA Methylation Analysis Identifies Differentially Methylated Sites Associated with Early-Onset Intracranial Atherosclerotic Stenosis
- Source :
- Journal of Atherosclerosis and Thrombosis
- Publication Year :
- 2020
- Publisher :
- Japan Atherosclerosis Society, 2020.
-
Abstract
- Aim: Studies have suggested that genetic and environmental factors do not account for all risks and mechanisms of intracranial atherosclerotic stenosis (ICAS). DNA methylation may play a role in the progression of ICAS. Methods: DNA methylation profiles of peripheral blood leucocytes from 7 patients with early-onset ICAS and 7 perfectly matched controls were interrogated for the first time using the Illumina Infinium Human MethylationEPIC BeadChip. Afterward, functional analysis for differentially methylated genes was conducted. In addition, pyrosequencing verification was performed in an independent cohort comprising 21 patients with earlyonset ICAS and 21 age- and gender-matched controls. Results: A total of 318 cytosine-phosphate-guanine sites were found to be differentially methylated based on the established standards. Functional analysis annotated differentially methylated sites to atherosclerosis-related processes and pathways, such as the negative regulation of hydrolase activity (GO 0051346), type II diabetes mellitus (KEGG hsa04930), and the insulin signaling pathway (KEGG hsa04910). In addition, a differentially methylated site was also validated, cg22443212 in gene Rnf213, which showed significant hypermethylation in patients with early-onset ICAS compared with controls 59.56% (49.77%, 88.55%) vs. 44.65% (25.07%, 53.21%), respectively; P = 0.010). Receiver operating characteristic curve analysis showed that the area under the curve value of cg22443212 was 0.744 (95% confidence interval, 0.586–0.866; P = 0.002). Conclusions: We revealed that altered DNA methylation may play a role in the occurrence and development of ICAS. These results provided new epigenetic insights into ICAS.
- Subjects :
- Male
Atherosclerotic stenosis
030204 cardiovascular system & hematology
Ring finger protein 213
Epigenesis, Genetic
Andrology
03 medical and health sciences
0302 clinical medicine
Internal Medicine
Humans
Medicine
Epigenetics
KEGG
Intracranial atherosclerotic stenosis
Gene
DNA methylation
Receiver operating characteristic
business.industry
Biochemistry (medical)
Area under the curve
Middle Aged
Intracranial Arteriosclerosis
3. Good health
Pyrosequencing
CpG Islands
Female
Original Article
Cardiology and Cardiovascular Medicine
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 18803873 and 13403478
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Atherosclerosis and Thrombosis
- Accession number :
- edsair.doi.dedup.....199d973f675e22bbddd4fbed62d1ce17