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Pérusse, Louis

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Pérusse

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Louis

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Université Laval. Département de kinésiologie

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ncf10139306

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Voici les éléments 1 - 10 sur 31
  • PublicationAccès libre
    Methylation quantitative trait loci within the TOMM20 gene are associated with metabolic syndrome-related lipid alterations in severely obese subjects
    (BioMed Central Ltd., 2016-07-29) Toro Martin, Juan de; Guénard, Frédéric; Pérusse, Louis; Hould, Frédéric-Simon; Marceau, Picard; Vohl, Marie-Claude; Deshaies, Yves; Lebel, Stéfane; Tchernof, André
    Background : The TOMM20 gene was previously identified as differentially expressed and methylated between severely obese subjects with and without metabolic syndrome (MS). Since metabolic complications do not affect all obese patients to the same extent, the aim of this study was to identify methylation quantitative trait loci (meQTL) potentially associated with MS-related complications within the TOMM20 locus. Methods : Methylation profiling, SNP genotyping and meQTL association tests (general linear models) were performed in a population of 48 severely obese subjects. Genotyping was extended to a larger population of 1720 severely obese subjects with or without MS, where genotype- and diplotype-based association tests were assessed by logistic regression. In silico analyses were performed using TRAP. Results : Four SNPs were identified as significant meQTLs for the differentially methylated site cg16490124. Individuals carrying rare alleles of rs4567344 (A > G) (P = 4.9 × 10−2) and rs11301 (T > C) (P = 5.9 × 10−3) showed decreased methylation levels at this site, whereas those carrying rare alleles of rs4551650 (T > C) (P = 3.5 × 10−15) and rs17523127 (C > G) (P = 3.5 × 10−15) exhibited a significant increase in methylation. rs4567344 and rs11301 were associated with increased susceptibility to exhibit high plasma triglycerides (TG ≥ 1.69 mmol/L), while rare alleles of rs4551650 and rs17523127 were significantly more represented in the low plasma total-C group (total-C ≤ 6.2 mmol/L). Haplotype reconstruction with the four meQTLs (rs4567344, rs11301, rs4551650, rs17523127) led to the identification of ten different diplotypes, with H1/H2 (GCGG/ACGG) exhibiting a nearly absence of methylation at cg16490124, and showing the highest risk of elevated plasma TG levels [OR = 2.03 (1.59–3.59)], a novel association with elevated LDL-cholesterol [OR = 1.86 (1.06–3.27)] and the complete inversion of the protective effect on total-C levels [OR = 2.03 (1.59–3.59)], especially in men. In silico analyses revealed that rs17523127 overlapped the CpG site cg16490124 and encompassed the core binding sites of the transcription factors Egr 1, 2 and 3, located within the TOMM20 promoter region. Conclusion : This study demonstrates that TOMM20 SNPs associated with MS-related lipid alterations are meQTLs potentially exerting their action through a CpG methylation-dependent effect. The strength of the diplotype-based associations may denote a novel meQTL additive action and point to this locus as particularly relevant in the inter-individual variability observed in the metabolic profiles of obese subjects.
  • PublicationRestreint
    Long-term adiposity changes are related to a glucocorticoid receptor polymorphism in young females
    (Oxford Academic, 2003-07-01) Drapeau, Vicky; Bouchard, Claude; Pérusse, Louis; Tremblay, Angelo; Bouchard, Luigi; Després, Jean-Pierre
    Male and female preadolescents and adolescents who participated in phase 1 of the Québec Family Study, and who were retested about 12 yr later, were recruited and subdivided on the basis of a genetic variant within the intron 2 of the glucocorticoid receptor (GRL IVS2-BclI). The increase in sc adiposity over the 12-yr follow-up period in the 4.5/2.3 genotype female subgroup was more than twice that observed in the 4.5/4.5 and the 2.3/2.3 genotype subgroups (P < 0.01). The statistical significance of this difference was essentially unchanged after adjusting for changes, over time, in percent dietary energy as fat, alcohol consumption, and participation in vigorous physical activity. In male subjects, the same trend was found, but it did not reach statistical significance. In conclusion, this study suggests that a significant interaction effect exists between variation in the glucocorticoid receptor gene and body fat gain in female subjects experiencing the transition between adolescence and adulthood. Further research will, however, be necessary to characterize the lifestyle factors promoting fat accumulation, over time, among genetically susceptible individuals.
  • PublicationRestreint
    The PPAR-gamma P12A polymorphism modulates the relation between dietary fat intake and components of the metabolic syndrome : results from the Quebec Family Study
    (Blackwell-synergy, 2003-03-10) Pérusse, Louis; Vohl, Marie-Claude; Després, Jean-Pierre; Robitaille, Julie
    The metabolic syndrome is a complex disorder characterized by an atherogenic dyslipidemia resulting from the interaction between genetic and nutritional factors. The objective of this study was to examine in a cohort of 720 adults participating in the Québec Family Study (QFS) whether dietary fat interacts with the P12A polymorphism in the gene encoding the peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ), a nuclear factor that regulates lipid and glucose homeostasis. Carriers of the A12 allele had a higher body mass index (BMI), waist circumference, fat mass as well as subcutaneous adipose tissue and visceral adipose tissue (VAT) areas both assessed by computed tomography than P12/P12 homozygotes. Total fat and saturated fat intakes estimated from a 3‐day food record were significantly correlated with several components of the metabolic syndrome in P12/P12 homozygotes. None of these expected associations were observed among carriers of the A12 allele. Furthermore, in a model including the PPAR‐γ P12A polymorphism, fat intake, age and gender, PPAR‐γ P12A and its interaction with fat intake were associated with BMI and waist circumference. Similar results were obtained when saturated fat intake replaced total fat intake into the model. When the two genotype groups were further classified into quartiles of total fat or saturated fat intake and their characteristics compared, an increase in fat intake was associated with an increase in waist circumference in P12/P12 homozygotes but not in A12 carriers. There was no difference in the waist circumference in carriers of the A12 allele whether the fat or the saturated fat intake was high or low. These results suggest that the PPAR‐γ P12A polymorphism can modulate the association between dietary fat intake and components of the metabolic syndrome.
  • PublicationAccès libre
    A GWAS follow-up of obesity-related SNPs in SYPL2 reveals sexspecific association with hip circumference
    (John Wiley & Sons Inc., 2016-09-20) Guénard, Frédéric; Biron, Simon; Toro Martin, Juan de; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Vohl, Marie-Claude; Deshaies, Yves; Marceau, Simon; Tchernof, André
    Objective A novel single-nucleotide polymorphism (SNP) associated with morbid obesity was recently identified by exome sequencing. The purpose of this study was to follow up this low-frequency coding SNP located within the SYPL2 locus and associated with body mass index in order to reveal novel associations with obesity-related traits. Methods The body mass index-associated SNP (rs62623713 A>G [chr1:109476817/hg19]) and two tagging SNPs within the SYPL2 locus, rs9661614 T>C (chr1:109479215) and rs485660 G>A (chr1:109480810), were genotyped in the obesity (n = 3,017) and the infogene (n = 676) cohorts, which were further combined, leading to a larger cohort of 3,693 individuals. Association testing was performed by general linear models in the obesity cohort and validated by joint analysis in the combined cohort. Results rs9661614 and rs485660 were significantly associated with hip circumference (HC) in the obesity cohort, with heterozygotes exhibiting a significantly lower HC. These results were validated by joint analysis for rs9661614 (false discovery rate [FDR]-corrected P = 7.5 × 10−4) and, to a lesser extent, for rs485660 (FDR corrected P = 3.9 × 10−2). The association with HC remained significant for rs9661614 when tested independently in women (FDR-corrected P = 1.7 × 10−2), but not for rs485660 (FDR-corrected P = 0.2). Both associations were absent in men. Conclusions This study reveals strong evidence for a novel association between rs9661614 (T>C) and HC in women, which likely reflects a preferential association of SYPL2 to a gynoid profile of fat distribution. The study findings support a clinical significance of SYPL2 worth considering when assessing risk factors associated with obesity.
  • PublicationRestreint
    Associations between dietary patterns and obesity phenotypes
    (Springer Nature, 2009-09-08) Paradis, Ann-Marie; Pérusse, Louis; Godin, Gaston; Vohl, Marie-Claude
    Objective: To examine whether dietary patterns are associated with obesity phenotypes. Design: Cross-sectional study. Subjects: We recruited 664 participants aged between 18 and 55 years. Dietary data were collected from a food frequency questionnaire. A factor analysis was performed to derive dietary patterns. Body mass index (BMI), weight and waist girth were recorded using standard procedures. Fat mass and fat-free mass were assessed by electrical bioimpedance. Obesity was defined as having a BMIX30 kg m2 and a positive FHO (FHO þ ) as having at least one obese first-degree relative. Results: Two dietary patterns were identified; Western and Prudent. The Western pattern was mainly characterized by a higher consumption of refined grains, French fries, red meats, condiments, processed meats and regular soft drinks whereas the Prudent pattern was mainly characterized by a higher consumption of non-hydrogenated fat, vegetables, eggs and fish and seafood. Subjects in the top tertile of the Western pattern had higher BMI, weight, waist girth, waist-to-hip ratio and fat mass than those in the lower tertile. In contrast, subjects in the top tertile of the Prudent pattern had lower BMI, weight, waist girth, fat mass, HDL-cholesterol levels, and lower triglyceride levels than those in the lowest tertile. Individuals in the upper tertile of the Western pattern were more likely to be obese (obesity was defined as having a BMIX30 kg m2) (OR ¼ 1.82, 95% CI 1.16–2.87) whereas those in the upper tertile of the Prudent pattern were less likely to be obese (OR ¼ 0.62, 95% CI 0.40–0.96). These latter significant associations were only observed among those with FHO þ . No such association was observed among FHO individuals. Conclusion: Individuals having a high score of Western pattern were more likely to be obese and those having a high score of the Prudent pattern were less likely to be obese, and this is particularly among individuals with an FHO+.
  • PublicationAccès libre
    Eating behaviors of non-obese individuals with and without familial history of obesity
    (Cambridge University Press, 2008-09-10) Paradis, Ann-Marie; Pérusse, Louis; Godin, Gaston; Lemieux, Simone; Vohl, Marie-Claude
    The aim of the present study was to examine whether eating behaviours and their subscales are associated with familial history of obesity (FHO) in a cohort of 326 non-obese men and women. Anthropometric measurements, eating behaviours (Three-Factor Eating Questionnaire) and dietary intakes (FFQ) have been determined in a sample of 197 women and 129 men. A positive FHO (FHO+) was defined as having at least one obese first-degree relative and a negative FHO (FHO-) as no obese first-degree relative. Men with FHO+ had higher scores of cognitive dietary restraint and flexible restraint than men with FHO-. In women, those with FHO+ had a higher score of disinhibition than women with FHO-. In both men and women, eating behaviours were not significantly associated with the number of obese family members. However, having an obese mother was associated with higher scores of cognitive dietary restraint, flexible restraint and rigid restraint in women. These findings demonstrate that eating behaviours of non-obese subjects are different according to the presence or absence of obese family members. More specifically, having an obese mother is associated with a higher dietary restraint score in women.
  • PublicationAccès libre
    Genetic regulation of differentially methylated genes in visceral adipose tissue of severely obese men discordant for the metabolic syndrome
    (Elsevier, 2017-02-01) Guénard, Frédéric; Biron, Simon; Biertho, Laurent; Pérusse, Louis; Lescelleur, Odette; Vohl, Marie-Claude; Marceau, Simon (***WMS); Deshaies, Yves; Tchernof, André
    A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTL) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. To pinpoint candidate genes for testing the association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. A genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. The genome-wide association study conducted to identify the SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations (P < 2.22 × 10−11) involving 2182 unique meQTLs regulating the methylation levels of 174 variable CpG sites. Two meQTLs disrupting CpG sites located within the collagen-encoding COL11A2 gene were tested for associations with MetS and its components in a cohort of 3021 obese individuals. Rare alleles of these meQTLs showed association with plasma fasting glucose levels. Further analysis conducted on these meQTL suggested a biological impact mediated through the disruption of transcription factor (TF)–binding sites based on the prediction of TF-binding affinities. The current study identified meQTL in the VAT of severely obese men and revealed associations of two COL11A2 meQTL with fasting glucose levels.
  • PublicationAccès libre
    Association between metabolite profiles, metabolic syndrome and obesity status
    (MDPI, 2016-05-27) Allam-Ndoul, Bénédicte; Guénard, Frédéric; Cormier, Hubert; Garneau, Véronique; Pérusse, Louis; Barbier, Olivier; Vohl, Marie-Claude
    Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.
  • PublicationAccès libre
    The rare allele of DGKZ SNP rs10838599 is associated with variability in HDL-cholesterol levels among severely obese patients
    (Open Access Text Pvt. Ltd, 2016-05-12) Guénard, Frédéric; Pérusse, Louis; Hould, Frédéric-Simon; Deshaies, Yves; Marceau, Picard; Bégin, Stéphanie; Vohl, Marie-Claude; Lebel, Stéfane; Tchernof, André
    Introduction: Diacylglycerol kinase-zeta, one of the ten isoforms of DGKs expressed in mammals is an important enzyme of lipid metabolism. It catalyzes the interconversion of diacylglycerol and phosphatidic acid, two major second messengers. Its gene DGKZ has been previously identified as being overexpressed and undermethylated in visceral adipose tissue of patients with (MetS+) versus without (MetS-) the metabolic syndrome (MetS). Objective: The aim of this study was to investigate the associations between DGKZ gene polymorphisms (SNPs) and phenotypes related to MetS (BMI, waist girth, CRP, fasting glucose, lipid profile (triglycerides, total-cholesterol, LDL-cholesterol and HDL-cholesterol (HDL-C)), resting systolic and diastolic blood pressures). Methods: The study sample included 1752 severely obese participants who underwent bariatric surgery. Associations between the five selected tSNPs of DGKZ and features of the MetS were tested. The effects of these SNPs on DGKZ methylation and expression levels were tested in subgroups of 32 and 14 obese subjects, respectively. Correlations between methylation and expression levels were also computed. Results: Homozygotes for the rare allele of rs10838599 displayed higher plasma HDL-C concentrations compared to the other genotype groups (p=0.03). For gene methylation, only a trend with the cg05412031 CpG site (p=0.09) was found for the single significantly phenotype-associated SNP. There was no significant correlation between DGKZ methylation at cg05412031 and expression levels. Conclusion: These results suggest that DGKZ SNP rs10838599 modulates plasma HDL-C levels thereby its gene contributes to the inter-individual variability observed in the cardiometabolic risk profile of patients with severe obesity.
  • 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.