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Genome-wide analysis of DNA methylation identifies S100A13 as an epigenetic biomarker in individuals with chronic (? 30?years) type 2 diabetes without diabetic retinopathy.

ABSTRACT: BACKGROUND:This study aimed to determine the epigenetic biomarkers of diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). This retrospective study is based on the Shanghai Xinjing community prevention and treatment administrative system of chronic diseases. The subjects enrolled herein were T2DM patients who had undergone long-term follow-up evaluation in the system. Two consecutive studies were conducted. In the discovery cohort, among 19 subjects who had developed DR with a DM duration < 3?years and 21 subjects without DR > 30?years after being diagnosed with DM, an Infinium Human Methylation 850 Beadchip was used to identify differential methylation regions (DMRs) and differential methylation sites (DMSs). The function of the genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis, and pathway network analysis. In the replication cohort, 87 DR patients with a short DM duration and 89 patients without DR over a DM duration > 20?years were compared to assess the association between DMSs and DR upon pyrosequencing. RESULTS:A total of 34 DMRs were identified. Genes containing DMSs with the top 5 highest beta value differences between DR and non-DR participants were located on chromosome 1 and were present in the S100A13 gene, which was associated with 71 GO terms. Two S100A13 gene sites, i.e., cg02873163 and cg11343894, displayed a good correlation with DR on pyrosequencing. CONCLUSIONS:DMSs in the S100A13 gene may be potential biomarkers of DR.

SUBMITTER: Li T

PROVIDER: S-EPMC7268721 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Genome-wide analysis of DNA methylation identifies S100A13 as an epigenetic biomarker in individuals with chronic (≥ 30 years) type 2 diabetes without diabetic retinopathy.

Li Tao T Xu Yi Y Shi Yongyong Y Chen Jianhua J Lin Senlin S Zhu Jianfeng J Xu Xian X Lu Lina L Zou Haidong H

Clinical epigenetics 20200603 1

<h4>Background</h4>This study aimed to determine the epigenetic biomarkers of diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). This retrospective study is based on the Shanghai Xinjing community prevention and treatment administrative system of chronic diseases. The subjects enrolled herein were T2DM patients who had undergone long-term follow-up evaluation in the system. Two consecutive studies were conducted. In the discovery cohort, among 19 subjects who had develop ...[more]

PMID: 32493412

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Project description:ObjectivesTo determine the risk factors for retinal microvascular impairment on optical coherence tomography angiography (OCT-A) in type 2 diabetic patients without clinical diabetic retinopathy (DR).MethodsThis retrospective and cross-sectional study enrolled 74 diabetic patients without clinically evident DR for the study group and 34 healthy subjects for the control group. OCT-A parameters were measured to determine vascular density (VD) and the foveal avascular zone (FAZ) size in the superficial and deep capillary plexuses (SCP/DCP) of the retina. Clinical data were collected on sex, age, diabetes duration, hemoglobin A1c (HbA1c), hypertension, dyslipidemia, low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR) and smoking status. Multiple linear regression analyses were performed to represent the associated clinical variables with OCT-A parameters in diabetic patients.ResultsIn comparison between the study and control groups, the VD in the SCP and DCP were significantly lower in diabetic patients compared to the controls (P = 0.022 and 0.003, respectively). The FAZ size in the SCP and DCP were significantly greater in diabetic patients compared to the controls (P = 0.035 and <0.001, respectively). In age- and sex-adjusted multiple regression analyses for the diabetic patients, dyslipidemia and hypertension were negatively associated with SCP-VD (β = -0.357, P = 0.002; β = -0.239, P = 0.039, respectively). Current smoking was correlated with lower DCP-VD (β = -0.255, P = 0.043). Greater SCP-FAZ size was associated with dyslipidemia and greater LDL-C (β = 0.254, P = 0.013; β = 0.232, P = 0.029, respectively), and greater DCP-FAZ size, with lower eGFR and greater LDL-C (β = -0.355, P = 0.004; β = 0.235, P = 0.037, respectively).ConclusionsDiabetic patients without clinical DR showed lower VD and greater FAZ size in the SCP and DCP compared to healthy controls. In diabetic patients without clinical DR, dyslipidemia and/or high LDL-C were important risk factors for retinal microvascular impairment. Hypertension, current smoking and lower eGFR also contributed to microvascular impairment.

Dataset Information

Genome-wide analysis of DNA methylation identifies S100A13 as an epigenetic biomarker in individuals with chronic (? 30?years) type 2 diabetes without diabetic retinopathy.

Publications

Genome-wide analysis of DNA methylation identifies S100A13 as an epigenetic biomarker in individuals with chronic (≥ 30 years) type 2 diabetes without diabetic retinopathy.

Similar Datasets

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