0000000000741022
AUTHOR
Pau Redon
MOESM12 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 12: Figure S4. Boxplots showing the DNA methylation beta values of the 36 common 0→5→10 dmCpGs described in Table 2.
Obesity and cardiovascular risk
: Obesity is a key factor for cardiovascular diseases and complications. Obesity is associated with hypertension, dyslipidemia and type II diabetes, which are the major predictors of cardiovascular disease in the future. It predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke that are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise,…
Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity part B obesity-induced cardiovascular disease, early prevention strategies and future research directions
: Obesity predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke, which are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.
Sympathetic neural activity, metabolic parameters and cardiorespiratory fitness in obese youths.
OBJECTIVE: The main objective of this cross-sectional study is to assess the cardiac autonomic neural activity in the presence of abnormally increased body weight in youths and its relationship to metabolic risk factors and cardiorespiratory fitness (CRF). METHODS: Sixty-four overweight and obese patients, aged 9-17 years, of both sexes, stratified according to the international BMI cut-off, were enrolled. Continuous ECG was recorded during 15 min in resting conditions, and the heart rate variability (HRV) was measured in the time domain, frequency domain and for nonlinear dynamics. In addition, cardiometabolic risk factors and CRF in effort conditions were assessed. RESULTS: Among the over…
Evidences from Clinical Trials and Use of Antihypertensive Drugs in Children and Adolescents
In adults, when prescribing antihypertensive therapy, decisions regarding the choice of agent can be based upon evidence from clinical trials in large numbers of subjects, many of these having compared one class of agent with another. Whilst increased emphases on conducting drug trials in children and adolescents over the past 25 years have yielded important advances, and have tested the efficacy and safety of the various classes of antihypertensive agents, there remains a general lack of high quality long-term outcome data to guide choice of drug therapy for pediatricians managing HTN. As of today, certain clinical trials in children and adolescents have established the pharmacokinetics, p…
Relationship between body composition and postural control in prepubertal overweight/obese children: A cross-sectional study
Abstract Background Excess body weight during childhood causes reduced motor functionality and problems in postural control, a negative influence which has been reported in the literature. Nevertheless, no information regarding the effect of body composition on the postural control of overweight and obese children is available. The objective of this study was therefore to establish these relationships. Methods A cross-sectional design was used to establish relationships between body composition and postural control variables obtained in bipedal eyes-open and eyes-closed conditions in twenty-two children. Centre of pressure signals were analysed in the temporal and frequency domains. Pearson…
Determinants of Cardiometabolic Risk Factors in the First Decade of Life
The present prospective study assessed the association of birth weight (BW) and growth pattern on cardiometabolic risk factors in a cohort followed from birth to 10 years of age. One hundred and forty-five subjects (73 girls) who fulfilled the inclusion criteria and had all their data recorded at birth and at 5 years were enrolled. Of these, 100 (52 girls) also recorded data at 10 years. Anthropometric measurements, office and 24-hour blood pressure, and metabolic parameters were obtained. At 5 years, both BW and current weight were determinants of blood pressure and metabolic parameters; however, as the subjects got older, the impact of body size increased. Higher BW and maternal obesity i…
Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
[Background] Early life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies.
MOESM11 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 11: Figure S3. Treemap plots indicating the results of REViGO sematic analyses of significantly enriched (FDR < 0.05) gene ontology biological process terms for genes containing (a) hyper- and (b) hypomethylated 0→5 dmCpGs. The dmCpGs are grouped by annotated genomic location (see Table S1, column “annotation”, for the annotations; “promoter” is formed by collapsing “Distal promoter” and “Promoter (<= 1kb)”, “gene body” is formed by collapsing “3’ UTR”, “5’ UTR”, “Intron”, “Exon” and “Downstream”). See Table S6 for full results, including Molecular Function and Cellular Component terms.
Longitudinal study of DNA methylation during the first 5 years of life
[Background]: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. [Methods]: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects,…
Impact of ESH and AAP hypertension guidelines for children and adolescents on office and ambulatory blood pressure-based classifications.
The objective was to assess the differences between the 2016 European Society of Hypertension (ESH) and the 2017 American Academy of Pediatrics (AAP) hypertension (HTN) guidelines in the distribution of office blood pressure (BP) categories as well as in the office and ambulatory BP mismatches.The study included 4940 clinical evaluations performed in 2957 youth (5-18 years) of both sexes. BP and anthropometric parameters were measured following standard conditions. The classification of the BP measurements was normotension, high-normal, stages 1 and 2 HTN, following the criteria of both guidelines. In a subgroup of 2467 participants, 3941 office BP assessment was completed with 24-h ambulat…
Uric acid is linked to cardiometabolic risk factors in overweight and obese youths.
OBJECTIVE Observational studies have indicated that high levels of serum uric acid are associated with the risk of cardiovascular disease. The aim of the present study is to investigate the association of uric acid with individual cardiometabolic risk factors, as well as their degree of clustering, in overweight and moderate obese youth. METHODS Three hundred and thirty-three Caucasians of both sexes (149 women), from 5-18 years of age from those who underwent an assessment of overweight/obesity. Anthropometric parameters, office and 24-h blood pressure measurements and metabolic profile, including HDL-cholesterol, triglycerides, insulin, HOMA index and uric acid were assessed. RESULTS Uric…
Identifying poor cardiorespiratory fitness in overweight and obese children and adolescents by using heart rate variability analysis under resting conditions.
Background: Childhood obesity, including overweight, continues increasing worldwide affecting health expectancy, quality of life and healthcare expenditure. These subjects have higher probability of suffering or developing cardio metabolic risk factors. Recent studies have revealed cardiorespiratory fitness (CRF) as a valuable clinical parameter to identify these subjects and have even suggested cut-off values. However, evaluating CRF in overweight and obese youth can be difficult to implement, unfriendly and expensive. Objective: Develop a screening tool to identify high-risk subjects in a representative population of those attending overweight/obesity assessment programmes without prior i…
Gender-related differences in serum uric acid in treated hypertensive patients from central and east European countries: findings from the Blood Pressure control rate and CArdiovascular Risk profilE study.
OBJECTIVE: Hyperuricemia has been associated with high blood pressure (BP) values, diabetes mellitus, metabolic syndrome and chronic kidney disease (CKD). In the present study, we assessed the gender-related relationships between serum uric acid (SUA) and cardionephrometabolic variables in central and east European hypertensive patients. METHODS: A total of 3206 treated hypertensive patients with available SUA levels from the BP-CARE study was analyzed. Correlations among SUA, BP values, BP control, diabetes mellitus, metabolic syndrome and CKD were performed according to gender. RESULTS: Twenty-five percent of the whole population showed hyperuricemia (28% in women and 23% in men). These p…
MOESM10 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 10: Figure S2. a) Treemap plots indicating the results of REViGO sematic analyses of significantly enriched (FDR < 0.05) gene ontology biological process terms for genes that simultaneously contained 0→5 hyper- and hypomethylated dmCpGs. In total, 460 significant terms were found (see Table S6 for full results, including Molecular Function and Cellular Component terms, and also 5→10 dmCpG enrichments). b) Equivalent plots for genes containing, respectively, hyper- or hypomethylated dmCpGs, irrespective of those same genes also containing dmCpGs that changed in the opposite direction.
MOESM5 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 5: Figure S1. Boxplots indicating the distribution of absolute beta values of the DNA methylation changes for 0→5 and 5→10 hyper- and hypomethylated dmCpGs. Effect size is measured as median difference and Cliff’s delta.
MOESM13 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 13: Table S7. DNA methylation values obtained by bisulfite sequencing for 3 CpGs across the original 33 subjects (technical validation) and two independent longitudinal cohorts (biological validation).
MOESM4 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 4: Table S6. Gene ontology enrichment analysis of 0→5 and 5→10 dmCpGs. Enrichments were calculated from the difference between the dmCpGs obtained in each of the analyses and the GO ontology database by the R/Bioconductor package missMethyl. Ontologies for genes with 1) both hyper- and hypomethylated probes 2) exclusively either hyper- or hypomethyated and 3) from mapped hyper- or hypomethylated dmCpGs which did not take into account CpGs differentially methylated in the opposite direction in the same genes are included. Also included are the ontologies found when analyzing 0→5 dmCpGs grouped by gene region (promoter, exon, intron and gene body). All of the analyses include …
MOESM7 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 7: Table S3. Histone mark enrichment analysis of 0→5 and 5→10 dmCpGs. Enrichments were calculated based on differences between the dmCpGs obtained in each of the analyses and the full collection of Roadmap epigenomics hg19 regions integrated in the LOLA extended software. Corresponding array backgrounds were used for the different comparisons.
MOESM9 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 9: Table S5. Enhancer element enrichment analysis of 0→5 and 5→10 dmCpGs. Enrichments were calculated from the difference between the dmCpGs obtained in each of the analyses and the enhancer elements obtained from the EnhancerAtlas database. A customized LOLA database which included information related to the enhancers in the different tissues/cell lines and corresponding array backgrounds were used for the appropriate enrichment calculation.
MOESM6 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 6: Table S2. Blood cell-type compositions as predicted by the Houseman algorithm for the 33 samples.
MOESM3 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 3: Table S1. Lists of annotated 0→5 and 5→10 dmCpGs.
MOESM2 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 2: Table S8. Primer sequences for bisulfite sequencing of the validated CpGs.
MOESM8 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 8: Table S4. Chromatin state enrichment analysis of 0→5 and 5→10 dmCpGs. Enrichments were calculated based on differences between the dmCpGs obtained in each of the analyses and the hg19 chromatin segmentation regions (ChromHMM, 18 states) obtained from Roadmap and ENCODE consortia. A custom LOLA database including information related to the chromatin states in the different tissues/cell lines and corresponding array backgrounds were used for the correct enrichment calculation.
MOESM1 of Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
Additional file 1: Table S9. Clinical characteristics of the 18 subjects from the independent cohorts.