TY - JOUR
T1 - 5-Hydroxymethylcytosines in circulating cell-free DNA reveal vascular complications of type 2 diabetes
AU - Yang, Ying
AU - Zeng, Chang
AU - Lu, Xingyu
AU - Song, Yanqun
AU - Nie, Ji
AU - Ran, Ruoxi
AU - Zhang, Zhou
AU - He, Chuan
AU - Zhang, Wei
AU - Liu, Song Mei
N1 - Funding Information:
Employment or Leadership: X. Lu, Shanghai Epican Genetech Co. Ltd.; Y. Song, Shanghai Epican Genetech Co. Ltd.; C. He, a scientific founder of Accent Therapeutics, Inc. Consultant or Advisory Role: C. He, Accent Therapeutics, Inc.; W. Zhang, Shanghai Epican Genetech Co., Ltd. Stock Ownership: C. He, Accent Therapeutics, Inc., Shanghai Epican Genetech Co. Ltd.; W. Zhang, Shanghai Epican Genetech Co., Ltd.; X. Lu, Shanghai Epican Genetech Co. Ltd.; Y. Song, Shanghai Epican Genetech Co. Ltd. Honoraria: None declared. Research Funding: S.M. Liu, the National Natural Science Foundation of China (81972009, 81772276, 91753201, 81472023), and Health Commission of Hubei Province Scientific Research Project (WJ2019H005, WJ2019C002); W. Zhang, P30 CA060553 Career Development Fund from the National Institutes of Health; C. He, The University of Chicago Ludwig Center; Y. Yang, Program of Excellent Doctoral (Post Doctoral) of Zhongnan Hospital of Wuhan University (ZNYB2019013). Expert Testimony: None declared. Patents: The 5hmC-Seal technology was invented by C. He and was licensed by Shanghai Epican Genetech Co. Ltd. for clinical diagnosis and prognosis of human diseases from the University of Chicago, patent no. 8,741,567.
Funding Information:
S.M. Liu, the National Natural Science Foundation of China (81972009, 81772276, 91753201, 81472023), and Health Commission of Hubei Province Scientific Research Project (WJ2019H005, WJ2019C002); W. Zhang, P30 CA060553 Career Development Fund from the National Institutes of Health; C. He, The University of Chicago Ludwig Center; Y. Yang, Program of Excellent Doctoral (Post Doctoral) of Zhongnan Hospital of Wuhan University (ZNYB2019013).
Publisher Copyright:
© 2019 American Association for Clinical Chemistry.
PY - 2019
Y1 - 2019
N2 - 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, noninvasive 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: area under the curve (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, noninvasive approach that can be applied in the clinic to monitor the presence and severity of diabetic vascular complications.
AB - 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, noninvasive 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: area under the curve (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, noninvasive approach that can be applied in the clinic to monitor the presence and severity of diabetic vascular complications.
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U2 - 10.1373/clinchem.2019.305508
DO - 10.1373/clinchem.2019.305508
M3 - Article
C2 - 31575611
AN - SCOPUS:85074309178
VL - 65
SP - 1414
EP - 1425
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 11
ER -
