Dataset Information

DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.

ABSTRACT: Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG sites exhibit altered DNA methylation in human pancreatic islets, liver, adipose tissue, and skeletal muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02-1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75-0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c, fasting insulin, and triglyceride levels, and was increased in adipose tissue and blood from the diabetic twin among monozygotic twin pairs discordant for T2D. DNA methylation at the PHOSPHO1 locus cg02650017 in blood correlated positively with HDL levels, and was decreased in skeletal muscle from diabetic vs. non-diabetic monozygotic twins. DNA methylation of cg18181703 (SOCS3), cg11024682 (SREBF1), and cg19693031 (TXNIP) was not associated with future T2D risk in subjects from the Botnia prospective study.

SUBMITTER: Dayeh T

PROVIDER: S-EPMC4939923 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.

Dayeh Tasnim T Tuomi Tiinamaija T Almgren Peter P Perfilyev Alexander A Jansson Per-Anders PA de Mello Vanessa D VD Pihlajamäki Jussi J Vaag Allan A Groop Leif L Nilsson Emma E Ling Charlotte C

Epigenetics 20160505 7

Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG site ...[more]

PMID: 27148772

Similar Datasets

Project description:Inter-individual DNA methylation variations were frequently hypothesized to alter individual susceptibility to Type 2 Diabetes Mellitus (T2DM). Sequence-influenced methylations were described in T2DM-associated genomic regions, but evidence for direct, sequence-independent association with disease risk is missing. Here, we explore disease-contributing DNA methylation through a stepwise study design: first, a pool-based, genome-scale screen among 1169 case and control individuals revealed an excess of differentially methylated sites in genomic regions that were previously associated with T2DM through genetic studies. Next, in-depth analyses were performed at selected top-ranking regions. A CpG site in the first intron of the FTO gene showed small (3.35%) but significant (P = 0.000021) hypomethylation of cases relative to controls. The effect was independent of the sequence polymorphism in the region and persists among individuals carrying the sequence-risk alleles. The odds of belonging to the T2DM group increased by 6.1% for every 1% decrease in methylation (OR = 1.061, 95% CI: 1.032-1.090), the odds ratio for decrease of 1 standard deviation of methylation (adjusted to gender) was 1.5856 (95% CI: 1.2824-1.9606) and the sensitivity (area under the curve = 0.638, 95% CI: 0.586-0.690; males = 0.675, females = 0.609) was better than that of the strongest known sequence variant. Furthermore, a prospective study in an independent population cohort revealed significant hypomethylation of young individuals that later progressed to T2DM, relative to the individuals who stayed healthy. Further genomic analysis revealed co-localization with gene enhancers and with binding sites for methylation-sensitive transcriptional regulators. The data showed that low methylation level at the analyzed sites is an early marker of T2DM and suggests a novel mechanism by which early-onset, inter-individual methylation variation at isolated non-promoter genomic sites predisposes to T2DM.

Project description:BackgroundEpidemiology of type 2 diabetes (T2D) is affected by genetic and environmental factors. Deoxyribonucleic acid (DNA) methylation as a kind of epigenetic mechanism has been reported to affect the pathogenesis of T2D. Both global DNA methylation and candidate genes were observed differentially methylated and identified changes. Peripheral blood biomarkers could have significant clinical utility due to the noninvasive operation and showed efficacy in measuring T2D-related DNA methylation. Moreover, due to the reversible feature of DNA methylation, it can be an effective therapy for T2D.MethodsThis study will be conducted according to the preferred reporting items for systematic review and meta-analysis protocols 2015 statement. The protocol of this systematic review and meta-analysis was registered on international platform of registered systematic review and meta-analysis protocols (No. 202040136). The following electronic bibliographic databases will be searched from inception: EMBASE, MEDLINE, Web of Science, Cochrane Central, China National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database, and Clinical Trials (ClinicalTrials.gov). A search strategy will be developed using a combination of medical subheadings words and keywords related to T2D, human peripheral blood, and DNA methylation. Two reviewers will screen the literature, and a third reviewer will adjudicate in case of disagreements. All the data will be extracted by 2 independent reviewers. The Cochrane Risk of Bias Assessment Tool will be used to assess the bias of randomized controlled studies, and the Newcastle-Ottawa scale for nonrandomized controlled studies. All the assessment will be investigated by 2 independent reviewers. The overall quality of extracted data will be assessed by using the grading of recommendations, assessment, development, and evaluation assessment tool. Disagreements and conflicts will be resolved by discussing it with a third reviewer. The narrative synthesis and meta-analysis of all evidence will be performed as the main findings analyzed.

Dataset Information

DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.

Publications

DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets