Ultra-high dimensional variable selection with application to normative aging study: DNA methylation and metabolic syndrome

Yoon, Grace; Zheng, Yinan; Zhang, Zhou; Zhang, Haixiang; Gao, Tao; Joyce, Brian T.; Zhang, Wei; Guan, Weihua; Baccarelli, Andrea A.; Jiang, Wenxin; Schwartz, Joel; Vokonas, Pantel; Hou, Lifang; Liu, Lei

doi:10.1186/s12859-017-1568-1

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…Methylation of the cg18181703 locus in the SOCS3 gene, involved in leptin and insulin signaling, was also identified in a separate study, inversely correlated with BMI, triglycerides, and MetS but positively correlated with HDL-c levels [ 24 ]. Relevant to our findings, Yoon et al independently identified ABCG1 (cg06500161) as being associated with MetS (in a Caucasian Veteran population) using an Iterative Sure Independence Screening analysis approach [ 30 ]. ABCG1 cg06500161 has also been reported to be associated with fasting insulin (in Caucasian non-diabetic adults) [ 26 ], blood lipids, and adiposity traits [ 29 , 31 ].…”

Section: Discussionsupporting

confidence: 72%

Epigenome-wide association study of metabolic syndrome in African-American adults

Akinyemiju

Patki

et al. 2018

Clin Epigenet

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BackgroundThe high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies.MethodsData on metabolic syndrome and DNA methylation was assessed on 614 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead Chip assay on DNA extracted from buffy coat. Linear mixed effects regression models were used to examine the association between CpG methylation at > 450,000 CpG sites and metabolic syndrome adjusted for study covariates. Replication using DNA from a separate sample of 69 African-Americans, as well as meta-analysis combining both cohorts, was conducted.ResultsTwo differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17 (cg06638433; p value = 3.10 × 10− 7) and the ABCG1 gene on chromosome 21 (cg06500161; p value = 2.60 × 10− 8) were identified. Results for the ABCG1 gene remained statistically significant in the replication dataset and meta-analysis.ConclusionMetabolic syndrome was consistently associated with increased methylation in the ABCG1 gene in the discovery and replication datasets, a gene that encodes a protein in the ATP-binding cassette transporter family and is involved in intra- and extra-cellular signaling and lipid transport.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0483-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 72%

Epigenome-wide association study of metabolic syndrome in African-American adults

Akinyemiju

Patki

et al. 2018

Clin Epigenet

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“…A recent study has also shown that the correlation between BMI and ABCG1 gene expression in monocytes is partially mediated by DNA methylation [ 31 ]. Previous studies have demonstrated that methylation of ABCG1 CpG sites cg06500161 and cg27243685 in the blood is positively associated with plasma triglyceride concentration and could be linked to obesity and metabolic syndrome [ 28 , 33 , 48 – 52 ]. One possible explanation is that ABCG1 could regulate the bioavailability and the subsequent activity of lipoprotein lipase (LPL), a rate-limiting enzyme that hydrolyzes circulating triglyceride-rich lipoproteins [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease

Miroshnikova

Пантелеева

Pobozheva

et al. 2021

BMC Cardiovasc Disord

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Background Recent studies have focused on the potential role of epicardial adipose tissue (EAT) in the development of coronary artery disease (CAD). ABCA1 and ABCG1 transporters regulate cell cholesterol content and reverse cholesterol transport. We aimed to determine whether DNA methylation and mRNA levels of the ABCA1 and ABCG1 genes in EAT and subcutaneous adipose tissue (SAT) were associated with CAD. Methods Paired EAT and SAT samples were collected from 82 patients undergoing elective cardiac surgery either for coronary artery bypass grafting (CAD group, N = 66) or valve surgery (NCAD group, N = 16). ABCA1 and ABCG1 mRNA levels in EAT and SAT samples were analyzed using real time polymerase chain reaction, ABCA1 protein levels in EAT samples were assessed by western blotting. ABCA1 and ABCG1 DNA methylation analysis was performed in 24 samples from the CAD group and 9 samples from the NCAD group via pyrosequencing. Results DNA methylation levels in the ABCA1 promoter and ABCG1 cg27243685 and cg06500161 CpG sites were higher in EAT samples from patients with CAD compared with NCAD (21.92% vs 10.81%, p = 0.003; 71.51% vs 68.42%, p = 0.024; 46.11% vs 37.79%, p = 0.016, respectively). In patients with CAD, ABCA1 and ABCG1 DNA methylation levels were higher in EAT than in SAT samples (p < 0.05). ABCA1 mRNA levels in EAT samples were reduced in the subgroup of patients with CAD and concomitant carotid artery disease or peripheral artery disease compared with the NCAD group (p = 0.024). ABCA1 protein levels in EAT samples tended to be lower in CAD patients than in the NCAD group (p = 0.053). DNA methylation levels at the ABCG1 cg27243685 site positively correlated with plasma triglyceride concentration (r = 0.510, p = 0.008), body mass index (r = 0.556, p = 0.013) and waist-to-hip ratio (r = 0.504, p = 0.012) in SAT samples. Conclusion CAD is associated with ABCA1 and ABCG1 DNA hypermethylation in EAT. CAD with concomitant carotid artery disease or peripheral artery disease is accompanied by decreased ABCA1 gene expression in EAT. DNA methylation levels at the ABCG1 cg27243685 locus in SAT are associated with hypertriglyceridemia and obesity.

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“…Generally, methylation in the promoter region could enhance transcriptional inhibition, but the effect in gene region has not been conclusive [23]. As a metabolic disease interacting with environmental and genetic risks, T2DM was found to be associated with DNA methylation level changes at the whole genome [24] and CpG-labeled DNA methylation has also been found as a biomarker of metabolic syndrome [25]. At the same time, diabetes mellitus could lead to the change of the methylation level in specific tissues, such as adipose tissue, while the related differential genes are mainly related to cell cycle regulation and damage response [26].…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation in Calca Promoter Inhibited ASC Osteogenic Differentiation in Rats with Type 2 Diabetic Mellitus

Wang

Ding

Shi

et al. 2020

Stem Cells International

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The abnormal environment of type 2 diabetes mellitus (T2DM) leads to a substantial decrease in osteogenic function of stem cells. However, the gene sequence does not vary before and after disease for the patient. This phenomenon may be related to changes in osteogenesis-related gene expression caused by DNA methylation. In this study, we established T2DM models to extract adipose-derived stem cells (ASCs) for different gene identifications through DNA methylation sequencing. Specific fragments of methylation changes in the target gene (Calca) were identified by IGV analysis. CGRP was applied to compare the effects on ASCs-T2DM morphology via phalloidin staining, proliferation through CCK-8 assay, and osteogenic differentiation with osteogenic staining, qPCR, and repair of calvarial defect. Furthermore, 5-azacytidine (5-az) was used to intervene ASCs-T2DM to verify the relationship between the methylation level of the target fragment and expression of Calca. We found that the DNA methylation level of target fragment of Calca in ASCs-T2DM was higher than that in ASCs-C. CGRP intervention showed that it did not change the morphology of ASCs-T2DM but could improve proliferation within a certain range. Meanwhile, it could significantly enhance the formation of ALP and calcium nodules in ASCs-T2DM, increase the expression of osteogenesis-related genes in vitro, and promote the healing of calvarial defects of T2DM rat in a concentration-dependent manner. 5-az intervention indicated that the reduction of the methylation level in Calca target fragment of ASCs-T2DM indeed escalated the gene expression, which may be related to DNMT1. Taken together, the environment of T2DM could upregulate the methylation level in the promoter region of Calca and then decrease the Calca expression. The coding product of Calca revealed a promoting role for osteogenic differentiation of ASCs-T2DM. This result provides an implication for us to understand the mechanism of the decreased osteogenic ability of ASCs-T2DM and improve its osteogenic capacity.

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Ultra-high dimensional variable selection with application to normative aging study: DNA methylation and metabolic syndrome

Cited by 5 publications

References 29 publications

Epigenome-wide association study of metabolic syndrome in African-American adults

Epigenome-wide association study of metabolic syndrome in African-American adults

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease

Hypermethylation in Calca Promoter Inhibited ASC Osteogenic Differentiation in Rats with Type 2 Diabetic Mellitus

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