Endocrine Abstracts (2017) 49 EP551 | DOI: 10.1530/endoabs.49.EP551

Genome-wide DNA methylation analysis for type 2 diabetes mellitus and cardiovascular disease: from a 23-year follow-up in the Da Qing diabetes prevention study

Xiaonan Dong, Yanyan Chen & Guangwei Li

Department of Endocrinology, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Cardiovascular disease (CVD) is a serious complication of diabetes mellitus (DM) and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetes and CVD.

Objective: To assessed the alteration of DNA methylation in patients with/without diabetes but developed CVD in a cohort study of Chinese patients.

Methods: 40 patients were randomizely selected from diabetics/nondiabetics with/without CVD after 23 years follow-up, including 20 DM without CVD, 20 DM with CVD. Then a genome wide methylation analysis was conducted using the recently developed Illumina Infinium® Methylation EPIC BeadChip, and focusing on individual cytosines at CpG loci throughout the promoter regions.

Results: DNA methylation data was analyzed with RnBeads software, and we observed CpG sites in promoter area of CPT1C, CREB5, ACACB, OLR1, CXCL11 showing higher methylation levels and HADHB showing lower methylation levels in DM with CVD patients after enrolling top 500 regions among combined rank (combined P value <0.05, respectively). Singular Value Decomposition (SVD) analysis indicated that significant βvalue of DNA methylation correlated with patient BMI, fasting glucose, cholesterol, triglyceride. After adjusting for confounding factors, these CpG sites were correlated with fasting glucose. These genes were then clustered in Fatty acid degradation, Glucagon signaling pathway, Adipocytokine signaling pathway and PPAR signaling pathway according to KEGG analysis, which play a role in the synthesis of key enzyme in lipid metabolism.

Table 1. Baseline Characteristics.
Age, years 62.86±6.1565.57±8.40
*BMI, kg/m224.05±1.5226.53±3.36
Sex (M/F) 3/103/10
Age at Diagnosis41.5±6.5244.6±8.55
Duration T2D 2323
*Fasting glucose, mmol/l 8.65±3.7310.12±2.71
HbAlc, %8.63±2.258.9±0.98
Cholesterol, mmol/l 4.54±0.575.29±1.09
Triglyceride, mmol/l 1.17±0.451.21±0.89
Means ± SD *: P<0.05

Conclusion: Our results provide evidence that diabetic CVD is associated with methylation changes in metabolic pathway alterations in blood leukocyte DNA. These differences in methylation are worthy of further validation using larger cases of diabetic patients with and without cardiovascular disease.

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