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Turcot, Valérie

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Turcot

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Valérie

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Université Laval. Département des sciences des aliments et de nutrition

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Voici les éléments 1 - 6 sur 6
  • PublicationAccès libre
    Génétique et épigénétique du syndrome métabolique
    (2012) Turcot, Valérie; Vohl, Marie-Claude
    L'obésité viscérale est souvent associée à un profil métabolique détérioré, aussi défini comme un syndrome métabolique (SMet), et qui inclut une résistance à l'insuline, une dyslipidémie et une hypertension. Les individus obèses ne sont pas tous égaux face au développement du SMet et une dysfonction du tissu adipeux, de même qu'une susceptibilité génétique et épigénétique pourraient expliquer cette hétérogénéité. Une précédente analyse transcriptomique du tissu adipeux viscéral (TAV) a identifié plusieurs gènes différentiellement exprimés entre des hommes avec obésité sévère atteints (SMet+) ou non (SMet-) d'un SMet. Le principal objectif de cette thèse était d'identifier des variations génétiques et épigénétiques parmi des gènes différentiel lement exprimés dans le TAV entre des hommes SMet+ et SMet- et qui sont associées à une variabilité de l'expression génique et aux composantes du SMet chez des individus avec obésité sévère. Des associations significatives ont été observées entre une variation génétique des gènes interferon-gamma-inducible protein 30 (IFI30) et thymic stromal lymphopoietin (TSIP) avec l'hyperglycémie / diabète de type 2 et la pression artérielle, respectivement. Des niveaux plus faibles de méthylation globale de l'ADN du génome, en quantifiant la méthylation des éléments répétitifs du génome de type LINE-1, étaient associés avec un plus grand risque de SMet. Les pourcentages de méthylation près de l'exon 2 du gène dipeptidylpeptidase-4 (DPP4) étaient associés avec son expression génique dans le TAV et avec les concentrations de cholestérol-HDL, mais étaient semblables entre un plus grand groupe d'individus SMet+ et SMet- dans le TAV et les globules blancs périphériques. Finalement, une approche d'analyse in silico a été proposée afin de cibler des gènes candidats de l'obésité dont l'expression serait potentiellement régulée par la méthylation dans leur pomoteur. Cette dernière étude a été effectuée lors d'un stage à l'étranger et l'approche proposée serait applicable dans d'autres contextes pathologiques, dont le SMet. Cette thèse dresse donc un aperçu des connaissances actuelles sur la génétique et l'épigénétique du SMet et les résultats qui y sont présentés contribueront, à leur manière, à améliorer notre compréhension de la pathophysiologie du SMet, ainsi que la susceptibilité génétique et épigénétique à développer des complications métaboliques en présence d'obésité.
  • PublicationRestreint
    DPP4 gene DNA methylation in the omentum is associated with its gene expression and plasma lipid profile in severe obesity
    (The Obesity Society, 2012-09-06) Biron, Simon; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Turcot, Valérie; Faucher, Geneviève; Bélisle, Alexandre; Vohl, Marie-Claude; Marceau, Simon; Deshaies, Yves; Bouchard, Luigi; Tchernof, André
    Severely obese subjects with the metabolic syndrome (MS) have higher dipeptidyl peptidase‐4 (DPP4) expression in their visceral adipose tissue (VAT) compared to obese individuals without MS. We tested the hypothesis that methylation level of CpG sites in the DPP4 promoter CpG island in VAT was genotype‐dependent and associated with DPP4 mRNA abundance and MS‐related phenotypes. The VAT DNA was extracted in 92 severely obese premenopausal women undergoing biliopancreatic derivation for the treatment of obesity. Women were nondiabetic and none of them used medication to treat MS features. Cytosine methylation rates (%) of 102 CpG sites in the DPP4 CpG island were assessed by pyrosequencing of sodium bisulfite‐treated DNA. Methylation rates were >10% for CpG sites 94–102. Their mean methylation rate (%Meth94–102) was different between genotypes for DPP4 polymorphisms rs13015258 (P = 0.001), rs17848915 (P = 0.0004), and c.1926 G>A (P = 0.001). The %Meth94–102 correlated negatively with DPP4 mRNA abundance (r = −0.25, P < 0.05) and positively with plasma high‐density lipoprotein (HDL) cholesterol concentrations (r = 0.22, P < 0.05), whereas DPP4 mRNA abundance correlated positively with plasma total‐/HDL‐cholesterol ratio (r = 0.25; P < 0.05). In the VAT of nondiabetic severely obese women, genotype‐dependent methylation levels of specific CpG sites in the DPP4 promoter CpG island were associated with DPP4 gene expression and variability in the plasma lipid profile. Higher DPP4 gene expression in VAT and its relationship with the plasma lipid profile may be explained by actually unknown DPP4 biological effect or, to another extent, may also be a marker of VAT inflammation known to be associated with metabolic disturbances.
  • PublicationRestreint
    A polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals
    (Springer-Verlag, 2011-01-24) Pérusse, Louis; Turcot, Valérie; Faucher, Geneviève; Hould, Frédéric-Simon; Marceau, Picard; Vohl, Marie-Claude; Deshaies, Yves; Bouchard, Luigi; Lebel, Stéfane; Tchernof, André
    A previous expression profiling of visceral adipose tissue (VAT) revealed that the immune response gene interferon-gamma-inducible protein 30 (IFI30) gene was 1.72-fold more highly expressed in non-diabetic severely obese men with the metabolic syndrome as compared to those without. Given the importance of low-grade inflammation in obesity-related metabolic complications, we hypothesized that variants in the IFI30 gene are associated with cardiovascular disease (CVD) risk factors. A detailed genetic investigation was performed at the IFI30 locus by sequencing its promoter, exons and intron-exon junction boundaries using DNA of 25 severely obese men. Among the 21 sequence-derived single-nucleotide polymorphisms (SNPs), 5 tagged SNPs (covering 100% of the common SNPs identified) were genotyped in two independent samples of severely obese patients (total n = 1,283). Using a multistage experimental design, chi-square analyses and logistic regressions were performed to compare genotype frequencies and compute odds-ratios (OR) for low and high CVD risk groups (dyslipidemia, hyperglycemia/diabetes and hypertension). A significant association was observed with the non-synonymous SNP rs11554159 (p.R76Q), where GA individuals showed lower risk (OR = 0.67; P = 0.0009) for hyperglycemia/diabetes as compared to homozygotes for the major allele (GG). No association was observed between rs11554159 and VAT IFI30 mRNA levels (P = 0.81), and the expression levels were not correlated with fasting plasma glucose levels (P = 0.31) in 112 non-diabetic severely obese women. The localization of rs11554159 near the active site of IFI30 suggests a functional effect of this SNP. This study showed a novel association between rs11554159 (p.R76Q) polymorphism at the IFI30 locus and the risk of hyperglycemia/diabetes in severely obese individuals.
  • PublicationRestreint
    LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes.
    (Springer Nature, 2012-07-02) Biron, Simon; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Bélisle, Alexandre; Turcot, Valérie; Marceau, Simon; Vohl, Marie-Claude; Deshaies, Yves; Tchernof, André
    Background: Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT) of severely obese subjects with (MetS+) versus without (MetS-) metabolic syndrome (MetS). Long interspersed nuclear element 1 (LINE-1) elements DNA methylation levels (% meth) in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke. Aim: To test whether LINE-1%meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals. Methods: DNA was extracted from VAT of 34 men (MetS-: n = 14, MetS+: n = 20) and 152 premenopausal women (MetS-: n = 84; MetS+: n = 68) undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA. Results: The mean LINE-1%meth in VAT was of 75.8% (SD = 3.0%). Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β = -0.04; P = 0.03), diastolic blood pressure (β = -0.65; P = 0.03) and MetS status (β = -0.04; P = 0.004) after adjustments for the effects of age, sex, waist circumference (except for MetS status) and smoking. While dividing subjects into quartiles based on their LINE-1%meth (Q1 to Q4: lower %meth to higher %meth levels), greater risk were observed in the first (Q1: odds ratio (OR) = 4.37, P = 0.004) and the second (Q2: OR = 4.76, P = 0.002) quartiles compared to Q4 (1.00) when adjusting for age, sex and smoking. Conclusions: These results suggest that lower global DNA methylation, assessed by LINE-1 repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.
  • PublicationAccès libre
    Comparison of the dipeptidyl peptidase-4 gene methylation levels between severely obese subjects with and without the metabolic syndrome
    (BioMed Central Ltd., 2013-02-04) Pérusse, Louis; Turcot, Valérie; Deshaies, Yves; Hould, Frédéric-Simon; Marceau, Picard; Belisle, Alexandre; Vohl, Marie-Claude; Tchernof, André; Lebel, Stéfane
    Background : The dipeptidyl peptidase-4 (DPP4) enzyme is a novel adipokine potentially involved in the development of the metabolic syndrome (MetS). Previous observations demonstrated higher visceral adipose tissue (VAT) DPP4 gene expression in non-diabetic severely obese men with (MetS+) vs. without (MetS−) MetS. DPP4 mRNA abundance in VAT correlated also with CpG site methylation levels (%Meth) localized within and near its exon 2 (CpG94 to CpG102) in non-diabetic severely obese women, regardless of their MetS status. The actual study tested whether DPP4 %Meth levels in VAT are different between MetS− and MetS+ non-diabetic severely obese subjects, whether variable metabolic and plasma lipid profiles are observed between DPP4 %Meth quartiles, and whether correlation exists in DPP4 %Meth levels between VAT and white blood cells (WBCs). Methods : DNA was extracted from the VAT of 26 men (MetS−: n=12, MetS+: n=14) and 79 women (MetS−: n=60; MetS+: n=19), as well as from WBCs in a sub-sample of 17 women (MetS−: n=9; MetS+: n=8). The %Meth levels of CpG94 to CpG102 were assessed by pyrosequencing of sodium bisulfite-treated DNA. ANOVA analyses were used to compare the %Meth of CpGs between MetS− and MetS+ groups, and to compare the metabolic phenotype and plasma lipid levels between methylation quartiles. Pearson correlation coefficient analyses were computed to test the relationship between VAT and WBCs CpG94-102 %Meth levels. Results : No difference was observed in CpG94-102 %Meth levels between MetS− and MetS+ subjects in VAT (P=0.67), but individuals categorized into CpG94-102 %Meth quartiles had variable plasma total-cholesterol concentrations (P=0.04). The %Meth levels of four CpGs in VAT were significantly correlated with those observed in WBCs (r=0.55−0.59, P≤0.03). Conclusions : This study demonstrated that %Meth of CpGs localized within and near the exon 2 of the DPP4 gene in VAT are not associated with MetS status. The actual study also revealed an association between the %Meth of this locus with plasma total-cholesterol in severe obesity, which suggests a link between the DPP4 gene and plasma lipid levels.
  • PublicationRestreint
    Genetic contribution to C-reactive protein levels in severe obesity
    (Academic Press, 2011-12-01) Turcot, Valérie; Guénard, Frédéric; Faucher, Geneviève; Bouchard, Luigi; Hould, Frédéric-Simon; Garneau, Véronique; Marceau, Picard; Houde, Alain; Vohl, Marie-Claude; Tchernof, André; Deshaies, Yves; Lebel, Stéfane; Bergeron, Jean
    Obese individuals are characterized by a chronic, low-grade inflammatory state. Increased levels of C-reactive protein (CRP), a marker of inflammation, have been observed in subjects with the metabolic syndrome. We have previously reported that genes encoding proteins involved in the anti-inflammatory and immune response are differentially expressed in visceral adipose tissue of obese men with or without the metabolic syndrome. Among these genes, the interferon-gamma-inducible protein 30 (IFI30), CD163 molecule (CD163), chemokine (C-X-C motif) ligand 9 (CXCL9) and thymic stromal lymphopoietin (TSLP), were selected for further genetic analyses. The aim of the study was to verify whether IFI30, CD163, CXCL9 and TSLP gene polymorphisms contribute to explain the inter-individual variability of the inflammatory profile of obesity assessed by plasma high-sensitivity CRP concentrations. A total of 1185 severely obese individuals were genotyped for single nucleotide polymorphisms (SNPs) covering most of the sequence-derived genetic variability at the IFI30, CD163, CXCL9 and TSLP gene loci (total of 27 SNPs). Following measurement of plasma CRP levels, subjects were divided into two groups, low vs. high using the median value of plasma CRP levels (8.31 mg/L) as a cutoff point. Genotype frequencies were compared between groups. Associations between genotypes and plasma CRP levels (continuous variable) were also tested after adjustments for age, sex, smoking and BMI. The rs11554159 and rs7125 IFI30 SNPs showed a significant difference in genotype frequencies (p < 0.05) between subgroups of low vs. high plasma CRP levels (wild type homozygotes: rs11554159 = 47% vs. 55%, rs7125 = 31% vs. 24%, for low vs. high CRP groups, respectively). The association between rs11554159 and CRP levels as a continuous variable remained significant (p = 0.004). Both carriers of the GA and AA genotypes demonstrated, on average, a 13% lower CRP levels in comparison with GG homozygotes. No association was observed between SNPs in the CD163, CXCL9 and TSLP genes and CRP levels. The IFI30 rs11554159 polymorphism could partially explain the inter-individual variability observed in the inflammatory profile associated with obesity.