ArticleGenome biology2014
Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
143 citing papers in PubMed, 3 syntheses or guidelines pooled it, 270 citations in OpenAlex.
- The microbiota-gut-brain-epigenome axis as a novel therapeutic target for decoding postpartum depression.Frontiers in medicine · 2026Pooled it
- TIGER: The gene expression regulatory variation landscape of human pancreatic islets.Cell reports · 2021Pooled it
- Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank.PLoS genetics · 2021Pooled it
- DNA methylation changes and improved sleep quality in adults with obstructive sleep apnea and diabetes.BMJ open diabetes research & care · 2019Trial
- MicroRNA-Driven Regulation of β-Cell Function in Type 2 Diabetes: Molecular Mechanisms, Network Insights, and Translational Perspectives.Acta physiologica (Oxford, England) · 2026Review
- Human Islet miR-199a-5p and miR-214-3p Associate With Donor Age, BMI, and Sex and Mediate Cellular Aging in Islet-Derived Cells.Acta physiologica (Oxford, England) · 2026Article
- ROMO1 and mitochondrial complex II/SDH are required for spare respiratory capacity and glucose homeostasis in mice.Diabetologia · 2026Article
- The regulation of intrahepatic fatty acid partitioning within the human liver: the effect of sex.Clinical science (London, England : 1979) · 2026Review
- One-carbon metabolism and cardiovascular disease: Molecular mechanisms, genetic influences, and epigenetic regulation.Biochemistry and biophysics reports · 2026Review
- Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes.Endocrinology · 2026Article
- Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes.Nature metabolism · 2026Article
- New insights into sexual dimorphism in cardiometabolic health.Hormones (Athens, Greece) · 2026Review
- Article
- Whole-genome profiling of age- and sex-associated DNA methylation signatures in human plasma cell-free DNA.Communications medicine · 2025Article
- Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes.bioRxiv : the preprint server for biology · 2025Article
- Islet-intrinsic sex differences in inflammatory signaling contribute to autoimmune diabetes susceptibility.bioRxiv : the preprint server for biology · 2025Article
- Article
- How to measure and model cardiovascular aging.Cardiovascular research · 2025Review
- Evaluation of methylation changes in blood cells of COVID-19 patients as a biomarker of severity of the infection.BMC infectious diseases · 2025Article
- Exploring Tissue- and Sex-Specific DNA Methylation in Cattle Using a Pan-Mammalian Infinium Array.International journal of molecular sciences · 2025Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpigenetic factors regulate tissue-specific expression and X-chromosome inactivation. Previous studies have identified epigenetic differences between sexes in some human tissues. However, it is unclear whether epigenetic modifications contribute to sex-specific differences in insulin secretion and metabolism. Here, we investigate the impact of sex on the genome-wide DNA methylation pattern in human pancreatic islets from 53 males and 34 females, and relate the methylome to changes in expression and insulin secretion.
resultsGlucose-stimulated insulin secretion is higher in female versus male islets. Genome-wide DNA methylation data in human islets clusters based on sex. While the chromosome-wide DNA methylation level on the X-chromosome is higher in female versus male islets, the autosomes do not display a global methylation difference between sexes. Methylation of 8,140 individual X-chromosome sites and 470 autosomal sites shows sex-specific differences in human islets. These include sites in/near AR, DUSP9, HNF4A, BCL11A and CDKN2B. 61 X-chromosome genes and 18 autosomal genes display sex-specific differences in both DNA methylation and expression. These include NKAP, SPESP1 and APLN, which exhibited lower expression in females. Functional analyses demonstrate that methylation of NKAP and SPESP1 promoters in vitro suppresses their transcriptional activity. Silencing of Nkap or Apln in clonal beta-cells results in increased insulin secretion. Differential methylation between sexes is associated with altered levels of microRNAs miR-660 and miR-532 and related target genes.
conclusionsChromosome-wide and gene-specific sex differences in DNA methylation associate with altered expression and insulin secretion in human islets. Our data demonstrate that epigenetics contribute to sex-specific metabolic phenotypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.