Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets

Hall, Elin; Volkov, Petr; Dayeh, Tasnim; Esguerra, Jonathan L.S.; Salö, Sofia; Eliasson, Lena; Rönn, Tina; Bacos, Karl; Ling, Charlotte

doi:10.1186/s13059-014-0522-z

Cited by 215 publications

(261 citation statements)

References 92 publications

Supporting

Mentioning

230

Contrasting

Order By: Relevance

“…The majority of probes (99.2%) were greater than 5%, a level that has been previously used as a threshold while identifying sexbased differences [41]. Interestingly, and in contrast to our a priori hypothesis, 52.5% (n = 2296) probes were hypermethylated in males as compared with females (Table 2).…”

Section: Identification and Replication Of Differentially Methylated Prmentioning

confidence: 60%

“…Following normalization, probes containing a single nucleotide polymorphism in the assayed CpG dinucleotide, as well as those for which two or more single nucleotide polymorphisms were located in the probe sequence were removed. Last, probes on the Y chromosome were removed from this study as they were not comparable between male and female placental samples [41,42]. A total of n = 377,673 probes, representing 20,442 genes, remained for analysis.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

SExual Epigenetic Dimorphism in The Human Placenta: Implications for Susceptibility During The Prenatal Period

et al. 2017

View full text Add to dashboard Cite

Aim: Sex-based differences in response to adverse prenatal environments and infant outcomes have been observed, yet the underlying mechanisms for this are unclear. The placental epigenome may be a driver of these differences. Methods: Placental DNA methylation was assessed at more than 480,000 CpG sites from male and female infants enrolled in the extremely low gestational age newborns cohort (ELGAN) and validated in a separate US-based cohort. The impact of gestational age on placental DNA methylation was further examined using the New Hampshire Birth Cohort Study for a total of n = 467 placentas. Results: A total of n = 2745 CpG sites, representing n = 587 genes, were identified as differentially methylated (p < 1 × 10 -7 ). The majority (n = 582 or 99%) of these were conserved among the New Hampshire Birth Cohort. The identified genes encode proteins related to immune function, growth/transcription factor signaling and transport across cell membranes. Conclusion: These data highlight sex-dependent epigenetic patterning in the placenta and provide insight into differences in infant outcomes and responses to the perinatal environment.

show abstract

Section: Identification and Replication Of Differentially Methylated Prmentioning

confidence: 60%

Section: Resultsmentioning

confidence: 99%

SExual Epigenetic Dimorphism in The Human Placenta: Implications for Susceptibility During The Prenatal Period

et al. 2017

View full text Add to dashboard Cite

show abstract

“…These data are intriguing considering that progranulin expression in rat hippocampus was found to be under the control of estrogen 43. Although there have been numerous studies describing sex dimorphisms in gene methylation in peripheral blood, these studies have failed to specifically identify progranulin 44, 45. Nevertheless, it is especially interesting to consider this sex dimorphism as women are twice as likely to develop AD as men.…”

Section: Discussionmentioning

confidence: 98%

Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment

Cooper

Nachun

Dokuru

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveChanges in progranulin (GRN) expression have been hypothesized to alter risk for Alzheimer's disease (AD). We investigated the relationship between GRN expression in peripheral blood and clinical diagnosis of AD and mild cognitive impairment (MCI).MethodsPeripheral blood progranulin gene expression was measured, using microarrays from Alzheimer's (n = 186), MCI (n = 118), and control (n = 204) subjects from the University of California San Francisco Memory and Aging Center (UCSF‐MAC) and two independent published series (AddNeuroMed and ADNI). GRN gene expression was correlated with clinical, demographic, and genetic data, including APOE haplotype and the GRN rs5848 single‐nucleotide polymorphism. Finally, we assessed progranulin protein levels, using enzyme‐linked immunosorbent assay, and methylation status using methylation microarrays.ResultsWe observed an increase in blood progranulin gene expression and a decrease in GRN promoter methylation in males (P = 0.007). Progranulin expression was 13% higher in AD and MCI patients compared with controls in the UCSF‐MAC cohort (F 2,505 = 10.41, P = 3.72*10−5). This finding was replicated in the AddNeuroMed (F 2,271 = 17.9, P = 4.83*10−8) but not the ADNI series. The rs5848 SNP (T‐allele) predicted decreased blood progranulin gene expression (P = 0.03). The APOE4 haplotype was positively associated with progranulin expression independent of diagnosis (P = 0.04). Finally, we did not identify differences in plasma progranulin protein levels or gene methylation between diagnostic categories.InterpretationProgranulin mRNA is elevated in peripheral blood of patients with AD and MCI and its expression is associated with numerous genetic and demographic factors. These data suggest a role in the pathogenesis of neurodegenerative dementias besides frontotemporal dementia.

show abstract

“…Hall et al analyzed the impact of insulin secretion in human pancreatic islets and found that epigenetic changes were associated with sex-based differences in insulin secretion [39]. Liu et al concluded that females tend to have higher levels of DNA methylation on the X-chromosomes and the autosomal chromosomes in saliva cells [45].…”

Section: Introductionmentioning

confidence: 99%

“…Previous epigenome-wide studies demonstrated sex-specific DNA methylation differences in specific genes of several human tissues and cell types such as liver, heart, blood, pancreatic islets, brain, and saliva [38][39][40][41][42][43][44]. Hall et al analyzed the impact of insulin secretion in human pancreatic islets and found that epigenetic changes were associated with sex-based differences in insulin secretion [39].…”

Section: Introductionmentioning

confidence: 99%

Epigenome-Wide Association (DNA Methylation) Study of Sex Differences in Normal Human Kidney

Joseph¹,

George²,

Green-Knox³

et al. 2017

J Drug Metab Toxicol

View full text Add to dashboard Cite

Studies have identified epigenetic sex differences in several human tissues and have implicated epigenetic factors in the regulation of tissue-specific expression. Studies have also shown that women and men respond differently to various drugs, thereby influencing the pharmacokinetics, pharmacodynamics, adverse reactions, efficacy, and safety of a drug. Using Illumina Human Methylation450 BeadChip kit, we investigated the influence of sex on DNA methylation patterns in normal human kidneys (16 females and 15 males). We then related the methylome to mRNA expression levels in kidney structure/function and Drug Metabolizing Enzyme and Transporter (DMET) genes (32 females and 59 males). Our findings indicate that 429 methylated sites on autosomal chromosomes had significant sex-specific differences in the normal human kidney. Methylated sites in/near regions associated with DMET genes or with genes involved in renal structure/function and disease were identified for subsequent analysis. Validation of 2 DMETs genes (POR and ABCA3) and 2 renal structure/function/disease genes (LAMA5 and PLAT) exhibited significant sex-specific differences in mRNA expression. Our results highlight sitespecific sexual dimorphisms (epigenetic-based) in normal human kidney. Importantly, we provide a reference methylome for normal human kidney, which may be utilized to improve our understanding of renal disease and assessing the overall safety and effectiveness of a drug in the kidney.

show abstract

Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets

Cited by 215 publications

References 92 publications

SExual Epigenetic Dimorphism in The Human Placenta: Implications for Susceptibility During The Prenatal Period

SExual Epigenetic Dimorphism in The Human Placenta: Implications for Susceptibility During The Prenatal Period

Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment

Epigenome-Wide Association (DNA Methylation) Study of Sex Differences in Normal Human Kidney

Contact Info

Product

Resources

About