DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants

Kwon, Eun Jin; Lee, Hye Ah; You, Young Ah; Park, Hyesook; Cho, Su Jin; Ha, Eun Hee; Kim, Young Ju

doi:10.1097/md.0000000000004590

Cited by 15 publications

(28 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have shown that ( HNF4a ) belongs to the nuclear hormone receptor superfamily (NR2A1) and regulates obesity and metabolic profiles as a transcription factor. DNA methylation of HNF4a can improve triglyceride levels in the cord blood of preterm infants, and can increase the risk of metabolic‐related diseases in adulthood (Kwon et al, , ). Miura et al reported the role of HNF4A in the glucose stimulated insulin secretion by pancreatic β‐cells (Miura et al, ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis

Chen

Wang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

The molecular mechanism of liver fibrosis caused by hepatitis C virus (HCV) is not clear. The aim of this study is to understand the molecular mechanism of liver fibrosis induced by HCV and to identify potential therapeutic targets for hepatic fibrosis. We analyzed gene expression patterns between high liver fibrosis and low liver fibrosis samples, and identified genes related to liver fibrosis. We identified TAF1, HNF4A, and CALM2 were related to the development of liver fibrosis. HNF4A is important for hepatic fibrogenesis, and upregulation of HNF4A is an ideal choice for treating liver fibrosis. The gene expression of CALM2 is significantly lower in liver fibrosis samples than nonfibrotic samples. TAF1 may serve as a biomarker for liver fibrosis. The results were further validated by an independent data set GSE84044. In summary, our study described changes in the gene expression during the occurrence and development of liver fibrosis. The TAF1, HNF4A, and CALM2 may serve as novel targets for the treatment of liver fibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…DNA methylation of HNF4a can improve triglyceride levels in the cord blood of preterm infants, and can increase the risk of metabolicrelated diseases in adulthood (Kwon et al, 2016(Kwon et al, , 2018. Miura et al reported the role of HNF4A in the glucose stimulated insulin secretion by pancreatic β-cells (Miura et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis

Chen

Wang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Newborn cord blood is an effective biosample for epigenetic epidemiology studies. In published studies based on whole cord blood, DNA methylation associations were identified with prenatal antidepressant exposure [29], fetal growth restriction [30], and cord blood triglyceride levels [31]. Other studies elected to process and extract DNA from buffy coat, and identified associations between DNA methylation and maternal depression or anxiety [32], parental obesity [33], birth weight- for-gestational age [13], and prenatal mercury exposure [34].…”

Section: Discussionmentioning

confidence: 99%

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

et al. 2018

View full text Add to dashboard Cite

Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (P = 1.4 × 10; P = 2.9 × 10; P = 3.8 × 10; P = 4.2 × 10; P = 9.9 × 10, P = 1.3 × 10) and not with sample type (P>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted P<10). Estimated cell type proportions did not differ by sample type (P = 0.46), and estimated proportions were highly correlated between paired samples (r = 0.99). Differences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

show abstract

“…Newborn cord blood has often been used in epigenetic epidemiology studies. In whole cord blood, DNA methylation associations were identified with prenatal antidepressant exposure 26 , fetal growth restriction 27 , and cord blood triglyceride levels 28 . Other studies elected to process and extract DNA from buffy coat, and identified associations between DNA methylation and maternal depression or anxiety 29 , parental obesity 30 , birth weight-for-gestational age 13 , and prenatal mercury exposure 31 .…”

Section: Discussionmentioning

confidence: 99%

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

Dou

Schmidt

Benke

et al. 2017

Preprint

View full text Add to dashboard Cite

Abstract:Background: Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells by generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability.Objectives: To evaluate differences in cell composition and DNA methylation between buffy coat and whole cord blood samples.Methods: Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in 8 individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition.Results: DNA methylation PCs were associated with individual (PPC1=1.4x10 -9 ; PPC2=2.9x10 -5 ; PPC3=3.8x10 -5 ; PPC4=4.2x10 -6 ; PPC5=9.9x10 -13 ), and not with sample type (PPC1-5>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired individual samples ranged from r=0.66 to r=0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (5 sites had unadjusted P<10 -5 ). Estimated cell type proportions did not differ by sample type (P=0.86), and estimated cell counts were highly correlated between paired samples (r=0.99).Conclusions: Differences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

show abstract

DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants

Abstract: Supplemental Digital Content is available in the text

Cited by 15 publications

References 58 publications

Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis

Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

Contact Info

Product

Resources

About