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The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes

BACKGROUND: DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore...

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Autores principales: He, Yunbiao, Chen, Xia, Liu, Mingliang, Zuo, Lei, Zhai, Zhiyu, Zhou, Long, Li, Guangzhen, Chen, Li, Qi, Guolong, Jing, Chunxia, Hao, Guang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568935/
https://www.ncbi.nlm.nih.gov/pubmed/37828521
http://dx.doi.org/10.1186/s12920-023-01689-3
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author He, Yunbiao
Chen, Xia
Liu, Mingliang
Zuo, Lei
Zhai, Zhiyu
Zhou, Long
Li, Guangzhen
Chen, Li
Qi, Guolong
Jing, Chunxia
Hao, Guang
author_facet He, Yunbiao
Chen, Xia
Liu, Mingliang
Zuo, Lei
Zhai, Zhiyu
Zhou, Long
Li, Guangzhen
Chen, Li
Qi, Guolong
Jing, Chunxia
Hao, Guang
author_sort He, Yunbiao
collection PubMed
description BACKGROUND: DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design. METHODS: The participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively. RESULTS: In the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation. CONCLUSIONS: In this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01689-3.
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spelling pubmed-105689352023-10-13 The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes He, Yunbiao Chen, Xia Liu, Mingliang Zuo, Lei Zhai, Zhiyu Zhou, Long Li, Guangzhen Chen, Li Qi, Guolong Jing, Chunxia Hao, Guang BMC Med Genomics Research BACKGROUND: DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design. METHODS: The participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively. RESULTS: In the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation. CONCLUSIONS: In this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01689-3. BioMed Central 2023-10-12 /pmc/articles/PMC10568935/ /pubmed/37828521 http://dx.doi.org/10.1186/s12920-023-01689-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
He, Yunbiao
Chen, Xia
Liu, Mingliang
Zuo, Lei
Zhai, Zhiyu
Zhou, Long
Li, Guangzhen
Chen, Li
Qi, Guolong
Jing, Chunxia
Hao, Guang
The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes
title The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes
title_full The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes
title_fullStr The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes
title_full_unstemmed The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes
title_short The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes
title_sort potential dna methylation markers of cardiovascular disease in patients with type 2 diabetes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568935/
https://www.ncbi.nlm.nih.gov/pubmed/37828521
http://dx.doi.org/10.1186/s12920-023-01689-3
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