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| Status |
Public on Jan 31, 2020 |
| Title |
5-Hydroxymethylcytosines in Circulating Cell-free DNA Reveal Vascular Complications of Type 2 Diabetes |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
BACKGROUND: Long-term complications of type 2 diabetes (T2D), such as macrovascular and microvascular events, are the major causes for T2D-related disability and mortality. A clinically convenient, non-invasive approach for monitoring the development of these complications would improve the overall life quality of patients with T2D and help reduce healthcare burden through preventive interventions.
METHODS: A selective chemical labeling strategy for 5-hydroxymethylcytosines (5hmC-Seal) was used to profile genome-wide 5hmCs, an emerging class of epigenetic markers implicated in complex diseases including diabetes, in circulating cell-free DNA (cfDNA) from a collection of Chinese patients (n = 62). Differentially modified 5hmC markers between patients with T2D with and without macrovascular/microvascular complications were analyzed under a case-control design.
RESULTS: Statistically significant changes in 5hmC markers were associated with T2D-related macrovascular/microvascular complications, involving genes and pathways relevant to vascular biology and diabetes, including insulin resistance and inflammation. A 16-gene 5hmC marker panel accurately distinguished patients with vascular complications from those without (testing set: AUC = 0.85, 95%CI, 0.73-0.96), outperforming conventional clinical variables such as urinary albumin. In addition, a separate 13-gene 5hmC marker panel could distinguish patients with single complications from those with multiple complications (testing set: AUC = 0.84, 95%CI, 0.68-0.99), showing superiority over conventional clinical variables.
CONCLUSIONS: The 5hmC markers in cfDNA reflected the epigenetic changes in patients with T2D who developed macrovascular/microvascular complications. The 5hmC-Seal assay has the potential to be a clinically convenient, non-invasive approach that can be applied in the clinic to monitor the presence and severity of diabetic vascular complications.
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| Overall design |
Differential 5hmC markers between T2D patients with and without macrovascular/microvascular complications were analyzed in a Chinese patient cohort (n = 62).
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| Contributor(s) |
Zhang W, Liu S, He C, Yang Y, Zeng C |
| Citation(s) |
31575611 |
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| Submission date |
Jan 30, 2019 |
| Last update date |
May 01, 2020 |
| Contact name |
Wei Zhang |
| E-mail(s) |
wei.zhang1@northwestern.edu
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| Organization name |
Northwestern University
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| Department |
Preventive Medicine
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| Street address |
680 N Lake Shore Drive, Suite 1400
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (62)
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| Relations |
| BioProject |
PRJNA517967 |
| SRA |
SRP182983 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE125929_5hmC_Count_Matrix.csv.gz |
1.6 Mb |
(ftp)(http) |
CSV |
| GSE125929_Clinical.SampleInfo_V1.csv.gz |
695 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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