15 results on '"Bouchard L"'
Search Results
2. Placental NEGR1 DNA methylation is associated with BMI and neurodevelopment in preschool-age children.
- Author
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Breton, E, Gagné-Ouellet, V, Thibeault, K, Guérin, R, Van Lieshout, Rj, Perron, P, Hivert, Mf, and Bouchard, L
- Abstract
Studies have linked maternal pre-pregnancy obesity and hyperglycaemia with metabolic and neurodevelopmental complications in childhood. DNA methylation (DNAm) might enable foetal adaptations to environmental adversities through important gene loci. NEGR1 is involved in both energy balance and behaviour regulation. The aim of this study was to investigate associations between placental DNAm at the NEGR1 gene locus and childhood anthropometric and neurodevelopmental profiles in preschoolers. We analysed 276 mother-child dyads from Gen3G, a prospective birth cohort from Sherbrooke. At 3yo (40.4 ± 3.0 months), we measured body mass index (BMI) and the mothers reported on offspring neurobehavior using the Strengths and Difficulties Questionnaire (SDQ). We quantified DNAm levels at 30 CpGs at the NEGR1 locus using the MethylationEPIC Array in placental biopsies. DNAm at four CpGs located before NEGR1 second exon predicted child's BMI z-score (cg26153364: β=−0.16 ± 0.04; p=0.008, cg23166710: β=0.14 ± 0.08; p=0.03) and SDQ total score (cg04932878: β=0.22 ± 1.0; p= 3.0x10
−4 , cg16525738: β=−0.14 ± 0.18; p=0.01, cg23166710: β=−0.13 ± 0.36; p= 0.04), explaining 4.2% (p=0.003) and 7.3% (p= 1.3 x 10−4 ) of BMI-z and SDQ variances. cg23166710 was associated with both childhood phenotypes and correlated with NEGR1 placental expression (r=−0.22, p=0.04), suggesting its possible functional role. Together, maternal metabolic characteristics during pregnancy with NEGR1 DNAm levels explained 7.4% (p=4.2 x 10−4 ) of BMI-z and 14.2% (p=2.8 x 10−7 ) of SDQ variance at 3yo. This longitudinal study suggests that placental NEGR1 DNAm is associated with adiposity and neurodevelopment in preschool children and highlights its potential role in their comorbidity. [ABSTRACT FROM AUTHOR]- Published
- 2020
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3. Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns
- Author
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Allard, C, primary, Desgagné, V, additional, Patenaude, J, additional, Lacroix, M, additional, Guillemette, L, additional, Battista, MC, additional, Doyon, M, additional, Ménard, J, additional, Ardilouze, JL, additional, Perron, P, additional, Bouchard, L, additional, and Hivert, MF, additional
- Published
- 2015
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4. Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm.
- Author
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Clément AA, Lamarche D, Masse MH, Légaré C, Tai LH, Fleury Deland L, Battista MC, Bouchard L, and D'Aragon F
- Subjects
- Humans, AMP-Activated Protein Kinases genetics, AMP-Activated Protein Kinases metabolism, Cytokine Release Syndrome, Cytokines genetics, Cytokines metabolism, DNA Methylation, Gene Expression Profiling, Inflammation genetics, Inflammation Mediators metabolism, Proof of Concept Study, Tissue Donors, Circulating MicroRNA genetics, Circulating MicroRNA metabolism, MicroRNAs metabolism
- Abstract
Neurologically deceased organ donors (NDDs) generally display an immune response involving an intense production of pro-inflammatory cytokines referred to as the cytokine storm. The sudden surge of inflammatory mediators in circulation promotes tissue and organ damages and ultimately leads to poor transplant outcome. As microRNAs (miRNAs) are frequently proposed as key regulators of inflammation and are relatively stable in circulation, changes in their profiles could play a role in the onset of the cytokine storm in NDDs. In this proof-of-concept study, we sought to investigate differentially abundant circulating miRNAs in a temporal manner between neurological death and organ recovery and to assess the association between specific miRNAs and levels of inflammatory cytokines in blood. Plasma samples from five NDDs were obtained at multiple time points between organ donation consent and organ recovery. Using a time-course analysis and miRNA sequencing, we identified 32 plasma miRNAs fluctuating between consent and organ recovery (false discovery rate; q-value < 0.1). Eleven miRNAs relatively abundant (>100 reads) and detected in all samples were selected for further biological pathway analysis (miR-486-3p, miR-103a-3p, miR-106b-3p, miR-182-5p, miR-101-3p, miR-10a-5p, miR-125a-5p, miR-146b-5p, miR-26a-5p, miR-423-5p, miR-92b-3p). These miRNAs targeted genes such as c-JUN (TNF signalling pathway) and eEF2 (AMPK pathway), suggesting a potential role in regulation of inflammation. Our results contribute to a better understanding of the miRNAs dynamic after neurological death in organ donors and could potentially be used to predict the related early cytokine storm. Trial registration : ClinicalTrials.gov ID NCT03786991. Registered December 2018.
- Published
- 2022
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5. Early-pregnancy maternal body mass index is associated with common DNA methylation markers in cord blood and placenta: a paired-tissue epigenome-wide association study.
- Author
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Ghildayal N, Fore R, Lutz SM, Cardenas A, Perron P, Bouchard L, and Hivert MF
- Subjects
- Body Mass Index, Epigenesis, Genetic, Female, Fetal Blood metabolism, Humans, Hypothalamo-Hypophyseal System, Infant, Infant, Newborn, Pituitary-Adrenal System, Placenta metabolism, Pregnancy, Prospective Studies, DNA Methylation, Epigenome
- Abstract
Women entering pregnancy with elevated body mass index (BMI) face greater risk of adverse outcomes during pregnancy, delivery, and for their offspring later in life, potentially via epigenetics. If epigenetic programming occurs early during in utero development, the differential marks should be detectable in multiple tissues despite the known unique epigenetic profile in each.We used early-pregnancy BMI as reflection of maternal metabolic milieu exposure in peri-conception and early-pregnancy period. We analysed DNA methylation in paired cord blood and placenta samples among 437 newborns from Gen3G, a pre-birth prospective cohort of primarily European descent. We measured DNA methylation in both tissues across the genome in >720,000 CpG sites using the Illumina MethylationEPIC array. At each site, we used linear mixed models (LMMs) with an unstructured variance-covariance matrix to test for an association between maternal early-pregnancy BMI and DNA methylation in both tissues (modelled as M -values). We adjusted for tissue-specific covariates, offspring sex, gestational age at delivery, and maternal smoking and age.Women had a mean (SD) BMI of 25.4 (5.7) kg/m
2 measured at first trimester visit (mean=9.9 weeks). Early-pregnancy BMI was associated with differential DNA methylation levels in paired-tissue analyses at two sites: cg10593758 (β=0.0126, SE=0.0025; P =4.07e-7), annotated to CRHBP , and cg0762168 (β=-0.0094, SE=0.0018; P =2.78e-7), annotated to CCDC97 .Application of LMMs in DNA methylation data from distinct fetal-origin tissues allowed us to identify CpG sites at which early-pregnancy BMI may have an epigenetic 'programming' effect on overall fetus development. One site ( CRHBP ) may play a role in hypothalamic-pituitary-adrenal axis regulation.- Published
- 2022
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6. Comparison of Illumina 450K and EPIC arrays in placental DNA methylation.
- Author
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Fernandez-Jimenez N, Allard C, Bouchard L, Perron P, Bustamante M, Bilbao JR, and Hivert MF
- Subjects
- Adult, CpG Islands, Female, High-Throughput Nucleotide Sequencing standards, Humans, Oligonucleotide Array Sequence Analysis standards, Pregnancy, Reproducibility of Results, Sequence Analysis, DNA standards, DNA Methylation, High-Throughput Nucleotide Sequencing methods, Oligonucleotide Array Sequence Analysis methods, Placenta metabolism, Sequence Analysis, DNA methods
- Abstract
Illumina HumanMethylation450 BeadChip (450K) has been commonly used to investigate DNA methylation in human tissues. Recently, it has been replaced by Illumina HumanMethylationEPIC BeadChip (EPIC) covering over 850,000 CpGs distributed genome-wide. Many consortia have now datasets coming from both arrays and aspire to analyze the two together. The placenta shows a high number of intermediate methylation levels and is often investigated for obstetric/birth outcomes, and potentially for long-term programming in offspring. We performed a systematic comparison between the two arrays using 108 duplicate placental samples from Gen3G birth cohort. We find that placenta shows a high per-sample correlation between the arrays, and higher median correlations at individual CpGs than those reported for blood. We identify 26,340 probes with absolute difference in per cent methylation >10%. We conclude that EPIC and 450K placental data can be combined, and we provide two lists of CpGs that should be excluded to avoid misleading results.
- Published
- 2019
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7. Locus-specific DNA methylation prediction in cord blood and placenta.
- Author
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Ma B, Allard C, Bouchard L, Perron P, Mittleman MA, Hivert MF, and Liang L
- Subjects
- CpG Islands, Female, Humans, Machine Learning, Organ Specificity, Pregnancy, DNA Methylation, Fetal Blood metabolism, Genetic Loci, Models, Genetic, Placenta metabolism
- Abstract
DNA methylation is known to be responsive to prenatal exposures, which may be a part of the mechanism linking early developmental exposures to future chronic diseases. Many studies use blood to measure DNA methylation, yet we know that DNA methylation is tissue specific. Placenta is central to fetal growth and development, but it is rarely feasible to collect this tissue in large epidemiological studies; on the other hand, cord blood samples are more accessible. In this study, based on paired samples of both placenta and cord blood tissues from 169 individuals, we investigated the methylation concordance between placenta and cord blood. We then employed a machine-learning-based model to predict locus-specific DNA methylation levels in placenta using DNA methylation levels in cord blood. We found that methylation correlation between placenta and cord blood is lower than other tissue pairs, consistent with existing observations that placenta methylation has a distinct pattern. Nonetheless, there are still a number of CpG sites showing robust association between the two tissues. We built prediction models for placenta methylation based on cord blood data and documented a subset of 1,012 CpG sites with high correlation between measured and predicted placenta methylation levels. The resulting list of CpG sites and prediction models could help to reveal the loci where internal or external influences may affect DNA methylation in both placenta and cord blood, and provide a reference data to predict the effects on placenta in future study even when the tissue is not available in an epidemiological study.
- Published
- 2019
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8. Placental lipoprotein lipase DNA methylation alterations are associated with gestational diabetes and body composition at 5 years of age.
- Author
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Gagné-Ouellet V, Houde AA, Guay SP, Perron P, Gaudet D, Guérin R, Jean-Patrice B, Hivert MF, Brisson D, and Bouchard L
- Subjects
- Adult, Child, Epigenesis, Genetic, Female, Humans, Infant, Newborn, Male, Pregnancy, Body Composition genetics, DNA Methylation, Diabetes, Gestational genetics, Lipoprotein Lipase genetics, Placenta metabolism
- Abstract
Gestational diabetes mellitus (GDM) is associated with obesity in childhood. This suggests that consequences of in utero exposure to maternal hyperglycemia extend beyond the fetal development, possibly through epigenetic programming. The aims of this study were to assess whether placental DNA methylation (DNAm) marks were associated with maternal GDM status and to offspring body composition at 5 years old in a prospective birth cohort. DNAm levels were measured in the fetal side of the placenta in 66 samples (24 from GDM mothers) using bisDNA-pyrosequencing. Anthropometric and body composition (bioimpedance) were measured in children at 5 years of age. Mann-Whitney and Spearman tests were used to assess associations between GDM, placental DNAm levels at the lipoprotein lipase (LPL) locus and children's weight, height, body mass index (BMI), body fat, and lean masses at 5 years of age. Weight, height, and BMI z-scores were computed according to the World Health Organization growth chart. Analyses were adjusted for gestational age at birth, child sex, maternal age, and pre-pregnancy BMI. LPL DNAm levels were positively correlated with birth weight z-scores (r = 0.252, P = 0.04), and with mid-childhood weight z-scores (r = 0.314, P = 0.01) and fat mass (r = 0.275, P = 0.04), and negatively correlated with lean mass (r = -0.306, P = 0.02). We found a negative correlation between LPL DNAm and mRNA levels in placenta (r = -0.459; P < 0.001), which highlights the regulation of transcriptional activity by these epivariations. We demonstrated that alterations in fetal placental DNAm levels at the LPL gene locus are associated with the anthropometric profile in children at 5 years of age. These findings support the concept of fetal metabolic programming through epigenetic changes.
- Published
- 2017
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9. Validation of a DNA methylation reference panel for the estimation of nucleated cells types in cord blood.
- Author
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Cardenas A, Allard C, Doyon M, Houseman EA, Bakulski KM, Perron P, Bouchard L, and Hivert MF
- Subjects
- Adult, CpG Islands genetics, Female, Genome, Human, Genome-Wide Association Study, Granulocytes metabolism, Humans, Infant, Newborn, Leukocyte Count, Monocytes metabolism, DNA Methylation genetics, Epigenomics, Erythroblasts metabolism, Fetal Blood metabolism
- Abstract
Cord blood is widely used as surrogate tissue in epigenome-wide association studies of prenatal conditions. Cell type composition variation across samples can be an important confounder of epigenome-wide association studies in blood that constitute a mixture of cells. We evaluated a newly developed cord blood reference panel to impute cell type composition from DNA methylation levels, including nucleated red blood cells (nRBCs). We estimated cell type composition from 154 unique cord blood samples with available DNA methylation data as well as direct measurements of nucleated cell types. We observed high correlations between the estimated and measured composition for nRBCs (r = 0.92, R
2 = 0.85), lymphocytes (r = 0.77, R2 = 0.58), and granulocytes (r = 0.72, R2 = 0.52), and a moderate correlation for monocytes (r = 0.51, R2 = 0.25) as well as relatively low root mean square errors from the residuals ranging from 1.4 to 5.4%. These results validate the use of the cord blood reference panel and highlight its utility and limitations for epidemiological studies.- Published
- 2016
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10. Variations in HDL-carried miR-223 and miR-135a concentrations after consumption of dietary trans fat are associated with changes in blood lipid and inflammatory markers in healthy men - an exploratory study.
- Author
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Desgagné V, Guay SP, Guérin R, Corbin F, Couture P, Lamarche B, and Bouchard L
- Subjects
- Adult, C-Reactive Protein metabolism, Cholesterol, HDL blood, Double-Blind Method, Humans, Male, MicroRNAs drug effects, Middle Aged, Trans Fatty Acids administration & dosage, Triglycerides blood, Diet, Lipoproteins, HDL blood, MicroRNAs blood, Trans Fatty Acids pharmacology
- Abstract
A high consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular diseases (CVDs). High-density lipoproteins (HDLs) have many cardioprotective properties and transport functional microRNAs (miRNAs) to recipient cells. We hypothesized that dietary TFAs modify the HDL-carried miRNA profile, therefore modulating its cardioprotective properties. We assessed whether consumption of dietary TFAs modifies HDL-carried miR-223-3p and miR-135a-3p concentration and the inter-relationship between diet-induced changes in HDL-carried miRNA concentration and CVD risk markers. In a double blind, randomized, crossover, controlled study, 9 men were fed each of 3 experimental isoenergetic diets: 1) High in industrial TFA (iTFA; 3.7% energy); 2) High in TFA from ruminants (rTFA; 3.7% energy); 3) Low in TFA (control; 0.8% energy) for 4 weeks each. HDLs were isolated by ultracentrifugation and miRNAs were quantified by RT-qPCR. Variations in HDL-miR-223-3p concentration were negatively correlated with variations in HDL-cholesterol after the iTFA diet (rs = 0.82; P = 0.007), and positively correlated with variations in C-reactive protein concentration after the rTFA diet (rs = 0.75; P = 0.020). Variations in HDL-miR-135a-3p concentration were positively correlated with variations in total triglyceride (TG) concentration following the iTFA diet (rs = -0.82; P = 0.007), and with variations in low-density lipoprotein (LDL)-TG concentration following the rTFA diet (rs = 0.83; P = 0.005), compared to the control diet. However, the consumption of dietary TFAs has no significant unidirectional impact on HDL-carried miR-223-3p and miR-135a-3p concentrations. Our results suggest that the variability in the HDL-carried miRNAs response to TFA intake, by being associated with variations in CVD risk factors, might reflect physiological changes in HDL functions.
- Published
- 2016
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11. Epipolymorphisms within lipoprotein genes contribute independently to plasma lipid levels in familial hypercholesterolemia.
- Author
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Guay SP, Brisson D, Lamarche B, Gaudet D, and Bouchard L
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 1, ATP-Binding Cassette Transporters blood, ATP-Binding Cassette Transporters genetics, Adult, Coronary Artery Disease blood, Coronary Artery Disease complications, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Genetic Loci, Humans, Hyperlipoproteinemia Type II blood, Hyperlipoproteinemia Type II complications, Lipase blood, Lipase genetics, Lipoproteins blood, Male, Middle Aged, Phospholipid Transfer Proteins blood, Phospholipid Transfer Proteins genetics, Scavenger Receptors, Class B blood, Scavenger Receptors, Class B genetics, Sex Factors, Cholesterol, HDL blood, Cholesterol, LDL blood, Hyperlipoproteinemia Type II genetics, Lipoproteins genetics, Polymorphism, Genetic, Triglycerides blood
- Abstract
Gene polymorphisms associated so far with plasma lipid concentrations explain only a fraction of their heritability, which can reach up to 60%. Recent studies suggest that epigenetic modifications (DNA methylation) could contribute to explain part of this missing heritability. We therefore assessed whether the DNA methylation of key lipoprotein metabolism genes is associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels in patients with familial hypercholesterolemia (FH). Untreated FH patients (61 men and 37 women) were recruited for the measurement of blood DNA methylation levels at the ABCG1, LIPC, PLTP and SCARB1 gene loci using bisulfite pyrosequencing. ABCG1, LIPC and PLTP DNA methylation was significantly associated with HDL-C, LDL-C and triglyceride levels in a sex-specific manner (all P<0.05). FH subjects with previous history of coronary artery disease (CAD) had higher LIPC DNA methylation levels compared with FH subjects without CAD (P = 0.02). Sex-specific multivariable linear regression models showed that new and previously reported epipolymorphisms (ABCG1-CpGC3, LIPC-CpGA2, mean PLTP-CpGC, LPL-CpGA3, CETP-CpGA2, and CETP-CpGB2) significantly contribute to variations in plasma lipid levels (all P<0.001 in men and P<0.02 in women), independently of traditional predictors such as age, waist circumference, blood pressure, fasting plasma lipids and glucose levels. These results suggest that epigenetic perturbations of key lipoprotein metabolism genes are associated with plasma lipid levels, contribute to the interindividual variability and might partially explain the missing heritability of plasma lipid levels, at least in FH.
- Published
- 2014
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12. Adaptations of placental and cord blood ABCA1 DNA methylation profile to maternal metabolic status.
- Author
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Houde AA, Guay SP, Desgagné V, Hivert MF, Baillargeon JP, St-Pierre J, Perron P, Gaudet D, Brisson D, and Bouchard L
- Subjects
- ATP Binding Cassette Transporter 1 genetics, Adult, Cholesterol, HDL blood, Epigenesis, Genetic, Female, Glucose Intolerance metabolism, Humans, Infant, Newborn, Maternal-Fetal Exchange, Pregnancy, Pregnancy Complications metabolism, Triglycerides blood, ATP Binding Cassette Transporter 1 metabolism, DNA Methylation, Fetal Blood metabolism, Metabolism, Placenta metabolism
- Abstract
In utero environmental perturbations have been associated with epigenetic changes in the offspring and a lifelong susceptibility to cardiovascular diseases (CVD). DNA methylation at the ATP-binding cassette transporter A1 (ABCA1) gene was previously associated with CVD, but whether these epigenetic marks respond to changes in the maternal environment is unknown. This study was undertaken to assess the associations between the maternal metabolic profile and ABCA1 DNA methylation levels in placenta and cord blood. Placenta and cord blood samples were obtained at delivery from 100 women including 26 with impaired glucose tolerance (IGT) diagnosed following a 75 g-oral glucose tolerance test (OGTT) between week 24 and 28 of gestation. ABCA1 DNA methylation and mRNA levels were measured using bisulfite pyrosequencing and quantitative real-time PCR, respectively. We report that ABCA1 DNA methylation levels on the maternal side of the placenta are correlated with maternal high density lipoprotein cholesterol (HDL-C) levels (r<-0.21; P<0.04) and glucose levels 2 h post-OGTT (r = 0.25; P = 0.02). On the fetal side of the placenta, ABCA1 DNA methylation levels are associated with cord blood triglyceride levels (r = -0.28; P = 0.01). ABCA1 DNA methylation variability on both sides of the placenta are also associated with ABCA1 mRNA levels (r<-0.35; P = 0.05). As opposed to placenta, cord blood DNA methylation levels are negatively correlated with maternal glucose 2 h post-OGTT (r = -0.26; P = 0.02). In conclusion, the epivariations observed in placenta and cord blood likely contribute to an optimal materno-fetal cholesterol transfer. These in utero epigenetics adaptations may also potentially trigger the long-term susceptibility of the newborn to dyslipidemia and CVD.
- Published
- 2013
- Full Text
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13. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases.
- Author
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Ruchat SM, Houde AA, Voisin G, St-Pierre J, Perron P, Baillargeon JP, Gaudet D, Hivert MF, Brisson D, and Bouchard L
- Subjects
- Adult, Birth Weight genetics, DNA Methylation, Diabetes, Gestational pathology, Epigenesis, Genetic, Epigenomics, Female, Fetal Blood metabolism, Gene Expression Regulation, Developmental, Humans, Infant, Newborn, Oligonucleotide Array Sequence Analysis, Placenta metabolism, Pregnancy, Signal Transduction genetics, Young Adult, Diabetes, Gestational genetics, Fetal Development genetics, Metabolic Diseases genetics
- Abstract
Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring's methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. DNA methylation was measured at>485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 × 10(-06); none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 ± 3.2% and 3.4 ± 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 × 10(-13)
- Published
- 2013
- Full Text
- View/download PDF
14. IGF2 DNA methylation is a modulator of newborn's fetal growth and development.
- Author
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St-Pierre J, Hivert MF, Perron P, Poirier P, Guay SP, Brisson D, and Bouchard L
- Subjects
- Adult, Arterial Pressure genetics, Birth Weight genetics, Blood Glucose genetics, Body Mass Index, Female, Fetal Blood metabolism, Humans, Insulin-Like Growth Factor II metabolism, Placenta metabolism, Pregnancy, Pregnancy Complications genetics, Pregnancy Complications metabolism, Pregnancy Complications pathology, RNA, Long Noncoding genetics, Somatomedins genetics, DNA Methylation genetics, Fetal Development genetics, Genomic Imprinting, Insulin-Like Growth Factor II genetics, Obesity genetics
- Abstract
The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity.
- Published
- 2012
- Full Text
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15. ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia.
- Author
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Guay SP, Brisson D, Munger J, Lamarche B, Gaudet D, and Bouchard L
- Subjects
- ATP Binding Cassette Transporter 1, ATP-Binding Cassette Transporters genetics, Adult, Aged, Cholesterol, HDL blood, Cholesterol, HDL genetics, Coronary Artery Disease metabolism, Coronary Artery Disease pathology, Epigenesis, Genetic, Exons, Female, Genetic Loci, Humans, Hyperlipoproteinemia Type II metabolism, Hyperlipoproteinemia Type II pathology, Male, Middle Aged, Mutation, Nucleotide Motifs, Phenotype, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, LDL blood, Receptors, LDL genetics, Receptors, LDL metabolism, Risk Factors, Young Adult, ATP-Binding Cassette Transporters metabolism, Cholesterol, HDL metabolism, Coronary Artery Disease genetics, DNA Methylation, Hyperlipoproteinemia Type II genetics, Promoter Regions, Genetic
- Abstract
High-density lipoproteins cholesterol (HDL-C) level, a strong coronary artery disease (CAD) clinical biomarker, shows significant interindividual variability. However, the molecular mechanisms involved remain mostly unknown. ATP-binding cassette A1 (ABCA1) catalyzes the cholesterol transfer from peripheral cells to nascent HDL particles. Recently, a differentially methylation region was identified in ABCA1 gene promoter locus, near the first exon. Therefore, we hypothesized that DNA methylation changes at ABCA1 gene locus is one of the molecular mechanisms involved in HDL-C interindividual variability. The study was conducted in familial hypercholesterolemia (FH), a monogenic disorder associated with a high risk of CAD . Ninety-seven FH patients (all p.W66G for the LDLR gene mutation and not under lipid-lowering treatment) were recruited and finely phenotyped for DNA methylation analyses at ABCA1 gene locus. ABCA1 DNA methylation levels were found negatively correlated with circulating HDL-C (r = -0.20; p = 0.05), HDL2-phospholipid levels (r = -0.43; p = 0.04), and with a trend for association with HDL peak particle size (r = -0.38; p = 0.08). ABCA1 DNA methylation levels were also found associated with prior history of CAD (CAD = 40.2% vs. without CAD = 34.3%; p = 0.003). These results suggest that epigenetic changes within the ABCA1 gene promoter contribute to the interindividual variability in plasma HDL-C concentrations and are associated with CAD expression. These findings could change our understanding of the molecular mechanisms involved in the pathophysiological processes leading to CAD.
- Published
- 2012
- Full Text
- View/download PDF
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