Genome-wide DNA methylation and transcriptome expression profiles of peripheral blood mononuclear cells in patients with systemic sclerosis with interstitial lung disease / 中南大学学报(医学版)

OBJECTIVES@#This study aims to investigate the genome-wide DNA methylation and transcriptome expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with systemic sclerosis (SSc) with interstitial lung disease (ILD), and to analyze the effects of DNA methylation on Wnt/β-catenin and chemokine signaling pathways.@*METHODS@#PBMCs were collected from 19 patients with SSc (SSc group) and 18 healthy persons (control group). Among SSc patients, there were 10 patients with ILD (SSc with ILD subgroup) and 9 patients without ILD (SSc without ILD subgroup). The genome-wide DNA methylation and gene expression level were analyzed by using Illumina 450K methylation chip and Illumina HT-12 v4.0 gene expression profiling chip. The effect of DNA methylation on Wnt/β-catenin and chemokine signal pathways was investigated.@*RESULTS@#Genome-wide DNA methylation analysis identified 71 hypermethylated CpG sites and 98 hypomethylated CpG sites in the SSc with ILD subgroup compared with the SSc without ILD subgroup. Transcriptome analysis distinguished 164 upregulated genes and 191 downregulated genes in the SSc with ILD subgroup as compared with the SSc without ILD subgroup. In PBMCs of the SSc group, 35 genes in Wnt/β-catenin signaling pathway were hypomethylated, while frizzled-1 (FZD1), mitogen-activated protein kinase 9 (MAPK9), mothers against DPP homolog 2 (SMAD2), transcription factor 7-like 2 (TCF7L2), and wingless-type MMTV integration site family, member 5B (WNT5B) mRNA expressions were upregulated as compared with the control group (all P<0.05). Compared with the SSc without ILD subgroup, the mRNA expressions of dickkopf homolog 2 (DKK2), FZD1, MAPK9 were upregulated in the SSc with ILD subgroup, but the differences were not statistically significant (all P>0.05). In PBMCs of the SSc group, 38 genes in chemokine signaling pathway were hypomethylated, while β-arrestin 1 (ARRB1), C-X-C motif chemokine ligand 10 (CXCL10), C-X-C motif chemokine ligand 16 (CXCL16), FGR, and neutrophil cytosolic factor 1C (NCF1C) mRNA expressions were upregulated as compared with the control group (all P<0.05). Compared with the SSc without ILD subgroup, the mRNA expressions of ARRB1, CXCL10, CXCL16 were upregulated in the SSc with ILD subgroup, but the differences were not statistically significant (all P>0.05).@*CONCLUSIONS@#There are differences in DNA methylation and transcriptome profiles between SSc with ILD and SSc without ILD. The expression levels of multiple genes in Wnt/β- catenin and chemokine signaling pathways are upregulated, which might be associatea with the pathogenesis of SSc.

Association between obesity and DNA methylation among the 7-16 year-old twins / 中华流行病学杂志

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.

Association of formaldehyde exposure,genome-wide DNA methylation,and childhood acute lymphocytic leukemia / 中国职业医学

OBJECTIVE: To explore the relationship of formaldehyde exposure, genome-wide DNA methylation, and prevalence of childhood acute lymphocytic leukemia( cALL).METHODS: A case-control study was conducted.Fifty-nine newly diagnosed cALL patients were selected as case group,and 54 orthopedic patients were included in control group.Enzyme-linked immunosorbent assay was used to measure the level of formaldehyde-human serum albumin( FA-HSA) and immunofluorescence method was used to examine the genome-wide DNA methylation level in whole blood.RESULTS: The level of FA-HAS in the blood of the case group was higher than that in the control group( median: 59.61 vs 35.06 fg/L,P < 0.01).Genomic-wide DNA methylation level in the case group was lower than that in the controls[( 2.86 ± 0.31) vs( 3.00 ± 0.28),P < 0.05].Formaldehyde exposure level was not associated with genomic-wide DNA methylation( Spearman correlation coefficient =-0.18,P > 0.05).High FA-HAS level and hypomethylation of genomic-wide DNA were risk factors for cALL onset( P < 0.05).CONCLUSION: Patients with high level of formaldehyde exposure and hypomethylation of genomic-wide DNA have a high risk of cALL.

Association between obesity and DNA methylation among the 7-16 year-old twins / 中华流行病学杂志

Objective On whole-genome scale,we tried to explore the correlation between obesity-related traits and DNA methylation sites,based on discordant monozygotic twin pairs.Methods A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district,Yanqing district and Fangshan district in Beijing in 2016.Information on twins was gathered through a self-designed questionnaire and results from physical examination,including height,weight and waist circumference of the subjects under study.DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip.R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes.Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs).VarFit function of emp irical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups.Results According to the obesity discordance criteria,we collected 23 pairs of twins (age range 7 to 16 years),including 12 male pairs.A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis.According to the significance level of FDR set as ＜0.05,no positive sites would meet this standard.When DMC CpG site cg05684382,with the smallest P value (1.26E-06) as on chromosome 12,the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16.Conclusions In this study,we analyzed the genome-wide DNA methylation and its correlation with obesity traits.After multiple testing corrections,no positive sites were found to have associated with obesity.However,results from the correlation analysis demonstrated sites cg05684382 (chr:12) and cg26188191 (chr:16) might have played a role in the development of obesity.This study provides a methodologic reference for the studies on discordance twins related problems.

DNA Methylation Profiles of Blood Cells Are Distinct between Early-Onset Obese and Control Individuals

Obesity is a highly prevalent, chronic disorder that has been increasing in incidence in young patients. Both epigenetic and genetic aberrations may play a role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic analyses will advance our understanding of the detailed molecular mechanisms underlying obesity and aid in the selection of potential biomarkers for obesity in youth. Here, we performed microarray-based DNA methylation and gene expression profiling of peripheral white blood cells obtained from six young, obese individuals and six healthy controls. We observed that the hierarchical clustering of DNA methylation, but not gene expression, clearly segregates the obese individuals from the controls, suggesting that the metabolic disturbance that occurs as a result of obesity at a young age may affect the DNA methylation of peripheral blood cells without accompanying transcriptional changes. To examine the genome-wide differences in the DNA methylation profiles of young obese and control individuals, we identified differentially methylated CpG sites and investigated their genomic and epigenomic contexts. The aberrant DNA methylation patterns in obese individuals can be summarized as relative gains and losses of DNA methylation in gene promoters and gene bodies, respectively. We also observed that the CpG islands of obese individuals are more susceptible to DNA methylation compared to controls. Our pilot study suggests that the genome-wide aberrant DNA methylation patterns of obese individuals may advance not only our understanding of the epigenomic pathogenesis but also early screening of obesity in youth.