Methylation of imprinted<i>IGF2</i>regions is associated with total, visceral, and hepatic adiposity in postmenopausal women

Song, Min-Ae; Ernst, Thomas; Tiirikainen, Maarit; Tost, Jörg; Wilkens, Lynne R.; Chang, Linda; Kolonel, Laurence N.; Marchand, Loı̈c Le; Lim, Unhee

doi:10.1080/15592294.2018.1518100

Cited by 6 publications

(7 citation statements)

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“…Research has shown that excessive levels of body fat, particularly intraabdominal fat, is a leading risk factor for the development of metabolic diseases. Furthermore, methylation levels of DMR regions in the IGF2 gene in leukocytes have been associated with total body fat content and the distribution of fat in the viscera and liver in manner that was independent of total adiposity [45]. These data are indicative of a potential association between IGF2 and PCOS.…”

Section: Discussionmentioning

confidence: 79%

Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study

et al. 2019

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Polycystic ovary syndrome (PCOS) represents a serious reproductive and endocrine condition and is associated with high incidence rates. H19 is a compelling long noncoding RNA (lncRNA) which carries out a range of biological functions. However, prior to this study, little was known as to whether there was an association between lncRNA H19 and PCOS. In the current study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine lncRNA H19 expression levels in peripheral blood leukocytes from patients with PCOS and compared this data with that derived from normal controls. We also screened data for potential relationships between lncRNA H19 and a range of endocrine variables in PCOS. The expression of lncRNA H19 was significantly higher in cases of PCOS than in controls. Individuals exhibiting higher expression levels of lncRNA H19 were associated with a significantly higher risk of PCOS than those with lower expression levels. Moreover, lncRNA H19 expression was positively correlated with fasting plasma glucose levels; this was the case with both raw data, and after adjustment for age and BMI in the PCOS group. However, lncRNA H19 expression showed no significant correlation with total testosterone or insulin resistance in either PCOS cases or the controls. In conclusion, we demonstrate the first evidence to indicate that lncRNA H19 is associated with PCOS, suggesting that elevated lncRNA H19 levels are a risk factor for PCOS. For susceptible individuals, lncRNA H19 may represent a useful biomarker of the early stages of endocrine and metabolic disorders in PCOS.

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Section: Discussionmentioning

confidence: 79%

Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study

et al. 2019

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“…33,57 There is evidence that epigenetic alteration at these DMRs from the early life environment is persistent-even into late adulthood 58 -and contributes to adverse health outcomes including low birth weight, adolescent adiposity, and adiposity in post-menopausal women. [34][35][36]57 While epigenetic regulation of IGF2 and H19 seem to play a role in obesity and metabolic conditions later in life, how or whether this starts to develop in childhood or adolescence is unknown. Examined separately, lower levels of dicarboxylic fatty acids have been previously associated with obesity in children 5,9 and H19 methylation is positively associated with adiposity including among 17-year old children.…”

Section: Discussionmentioning

confidence: 99%

“…These genes and the LINE-1 biomarker were selected due to evidence for environmental-lability by various exposures in early development 15 , 31 - 33 and for evidence of associations with adiposity-related outcomes in childhood or beyond. 34 - 36 …”

Section: Methodsmentioning

confidence: 99%

“…These genes and the LINE-1 biomarker were selected due to evidence for environmental-lability by various exposures in early development 15,[31][32][33] and for evidence of associations with adiposity-related outcomes in childhood or beyond. [34][35][36] Percent DNA methylation was quantified via the pyrosequencing platform 37 using assays previously developed by us for LINE-1 38 and HSD11B2 15 and by others for H19. 33 Details on each region are included in Supplemental Table S1.…”

Section: Assessment Of Dna Methylationmentioning

confidence: 99%

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Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort

et al. 2020

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Epigenetic modifications, such as DNA methylation, influence gene expression and cardiometabolic phenotypes that are manifest in developmental periods in later life, including adolescence. Untargeted metabolomics analysis provide a comprehensive snapshot of physiological processes and metabolism and have been related to DNA methylation in adults, offering insights into the regulatory networks that influence cellular processes. We analyzed the cross-sectional correlation of blood leukocyte DNA methylation with 3758 serum metabolite features (574 of which are identifiable) in 238 children (ages 8-14 years) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Associations between these features and percent DNA methylation in adolescent blood leukocytes at LINE-1 repetitive elements and genes that regulate early life growth ( IGF2, H19, HSD11B2) were assessed by mixed effects models, adjusting for sex, age, and puberty status. After false discovery rate correction (FDR q < 0.05), 76 metabolites were significantly associated with LINE-1 DNA methylation, 27 with HSD11B2, 103 with H19, and 4 with IGF2. The ten identifiable metabolites included dicarboxylic fatty acids (five associated with LINE-1 or H19 methylation at q < 0.05) and 1-octadecanoyl-rac-glycerol ( q < 0.0001 for association with H19 and q = 0.04 for association with LINE-1). We then assessed the association between these ten known metabolites and adiposity 3 years later. Two metabolites, dicarboxylic fatty acid 17:3 and 5-oxo-7-octenoic acid, were inversely associated with measures of adiposity ( P < .05) assessed approximately 3 years later in adolescence. In stratified analyses, sex-specific and puberty-stage specific (Tanner stage = 2 to 5 vs Tanner stage = 1) associations were observed. Most notably, hundreds of statistically significant associations were observed between H19 and LINE-1 DNA methylation and metabolites among children who had initiated puberty. Understanding relationships between subclinical molecular biomarkers (DNA methylation and metabolites) may increase our understanding of genes and biological pathways contributing to metabolic changes that underlie the development of adiposity during adolescence.

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“…Participants for this study were recruited from the Multiethnic Cohort Study (MEC; 1993-current) [4]. As detailed previously [20,21], in 2009-2019, 60 overall healthy, postmenopausal women aged 60-65 were recruited among the MEC participants in Oahu, Hawaii, including self-identified 30 European Americans (EUA) and 30 Japanese Americans (JPA) selected after stratification on age and BMI. This ancillary study within the MEC was a pilot study to explore imaging-based body composition of JPA, who were observed to have higher risks for obesityrelated diseases and cancers in the MEC [5,7,8] despite their lower mean BMI compared to EUA among generally healthy individuals.…”

Section: Study Participantsmentioning

confidence: 99%

Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study

et al. 2021

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Background Racial/ethnic disparities in health reflect a combination of genetic and environmental causes, and DNA methylation may be an important mediator. We compared in an exploratory manner the blood DNA methylome of Japanese Americans (JPA) versus European Americans (EUA). Methods Genome-wide buffy coat DNA methylation was profiled among healthy Multiethnic Cohort participant women who were Japanese (JPA; n = 30) or European (EUA; n = 28) Americans aged 60–65. Differentially methylated CpGs by race/ethnicity (DM-CpGs) were identified by linear regression (Bonferroni-corrected P < 0.1) and analyzed in relation to corresponding gene expression, a priori selected single nucleotide polymorphisms (SNPs), and blood biomarkers of inflammation and metabolism using Pearson or Spearman correlations (FDR < 0.1). Results We identified 174 DM-CpGs with the majority of hypermethylated in JPA compared to EUA (n = 133), often in promoter regions (n = 48). Half (51%) of the genes corresponding to the DM-CpGs were involved in liver function and liver disease, and the methylation in nine genes was significantly correlated with gene expression for DM-CpGs. A total of 156 DM-CpGs were associated with rs7489665 (SH2B1). Methylation of DM-CpGs was correlated with blood levels of the cytokine MIP1B (n = 146). We confirmed some of the DM-CpGs in the TCGA adjacent non-tumor liver tissue of Asians versus EUA. Conclusion We found a number of differentially methylated CpGs in blood DNA between JPA and EUA women with a potential link to liver disease, specific SNPs, and systemic inflammation. These findings may support further research on the role of DNA methylation in mediating some of the higher risk of liver disease among JPA.

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Methylation of imprintedIGF2regions is associated with total, visceral, and hepatic adiposity in postmenopausal women

Cited by 6 publications

References 60 publications

Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study

Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study

Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort

Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study

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