Génétique, acides gras oméga-3 et facteurs de risque des maladies cardiovasculaires

Les maladies chroniques telles que les maladies cardiovasculaires (MCV) sont complexes et leur risque est modulé par de nombreux facteurs tels que le bagage génétique et l’alimentation. Dans le cadre de ce projet, une cohorte de 210 participants a été recrutée. Deux profils alimentaires ont été identifiés, le profil Prudent caractérisé par une consommation plus élevée de légumes, fruits, produits céréaliers à grains entiers et de gras non-hydrogénés et le profil Western caractérisé par une consommation plus élevée de produits céréaliers raffinés, desserts, sucreries et viandes transformées. Ces deux profils alimentaires modulaient l’expression de gènes impliqués dans le système immunitaire, la réponse inflammatoire, le cancer et/ou les MCV. Le profil alimentaire Western était également associé à un profil de métabolites constitué de concentrations plus élevées de certains acides aminés et d’acylcarnitines à courtes chaînes. Afin d’étudier la variabilité interindividuelle dans la réponse à un nutriment, une supplémentation de 6 semaines en huile de poisson a été réalisée chez les 210 participants. Des SNPs de gènes reliés aux voies de la lipogénèse de novo et la bêta-oxydation des acides gras (ACLY, ACACA, GCK, RXRA, ACOX1) affectaient seuls, ou en interaction avec la diète, la réponse des triglycérides (TG) plasmatiques suite à la supplémentation en huile de poisson. La variabilité génétique présente dans le gène sterol regulatory element binding transcription factor 1 (SREBF1) expliquait une partie des différences interindividuelles observées dans la réponse des concentrations d’insuline suite à la supplémentation en huile de poisson. Dans une seconde cohorte de 691 individus, des associations entre des SNPs, identifiés à l’aide d’un GWAS réalisé sur la cohorte des 210 individus ayant pris la supplémentation en huile de poisson, et les concentrations de TG et d’acides gras dans les phospholipides plasmatiques ont été observées. Cette thèse comprend un volet d’application des connaissances où l’attitude a été identifiée comme le principal déterminant de l’intention des diététistes de discuter de nutrigénétique avec leurs patients/clients. Globalement, ces résultats démontrent que les profils alimentaires influencent le métabolisme à différents niveaux et que la réponse à l’huile de poisson peut être variable tout dépendamment du bagage génétique et de l’alimentation.Chronic diseases such as cardiovascular diseases (CVD) are complex and their risk factors are regulated by many factors, for example the genetic background and dietary intakes. In this project, 210 participants were recruited. Two dietary factors were identified, the Prudent dietary pattern which was characterised by higher intakes of vegetables, fruits, whole grain products and non-hydrogenated fats and the Western dietary pattern, characterised by higher intakes of refined grain products, desserts, sweets and processed meats. Both dietary patterns modulated the expression of genes related to the immune system, inflammatory response, cancer and/or CVD. The Western dietary pattern was also associated with a metabolite profile which comprised greater concentrations of certain amino acids as well as small chain acylcartinines. To examine the interindividual variability in the response to a nutrient, a 6 week fish oil supplementation was conducted among the 210 participants. SNPs related to genes involved in de novo lipogenesis and fatty acid beta-oxidation (ACLY, ACACA, GCK, RXRA, ACOX1) were associated alone or in an interaction effect with dietary intakes with the plasma triglyceride (TG) response to the fish oil supplementation. The genetic variability within sterol regulatory element binding transcription factor 1 (SREBF1) gene was associated with differences in the response of insulin concentrations following fish oil supplementation. In a second cohort of 691 participants, associations between SNPs, identified in a previous GWAS conducted among the 210 participants supplemented with fish oil, and TG as well as plasma phospholipid fatty acid concentrations were observed. This thesis also comprises a knowledge transfer section where the attitude was identified as the main determinant of the intention of dietitians to discuss nutrigenetics with their patients/clients. Globally, these results demonstrate that dietary patterns modulate the metabolism at several levels and that the response to fish oil is variable depending upon genetic profile and dietary intakes

L'effet de l'alimentation et de polymorphismes des gènes peroxisome proliferator-activated receptors sur la taille des particules LDL

En 2004, les maladies cardiovasculaires (MCV) causaient environ 72 000 décès au Canada. Le National Cholesterol Education Program reconnaît maintenant la taille des particules de lipoprotéines de faible densité (LDL) comme un facteur de risque émergeant. La taille des particules LDL peut être influencée par l'alimentation et la génétique. Celle-ci a été déterminée par électrophorèse sur gels de polyacrylamide. L'utilisation des profils alimentaires permet d'évaluer l'impact global de l'alimentation sur un facteur de risque. Les profils "Prudent" et "Western" ont été déterminés par analyse factorielle et associés à la taille des particules LDL. Les peroxisome proliferator-activated receptors (PPARs) sont des gènes connus pour avoir un effet sur la taille des particules LDL. Des effets d'interactions gènes-diète ont été observés pour les trois polymorphismes (PPARα L162V, PPARγ P12A et PPAR[delta] -87T>C) à l'étude. Ces résultats illustrent l'importance de considérer différents facteurs lors de l'étude des facteurs de risque de MCV

Évaluation du programme Accès à l’école : Évaluation des effets

Développé conjointement par des écoles et des centres de pédiatrie sociale, le programme Accès à l’école (AE) vise à soutenir l’enfant dans son expérience de la rentrée scolaire en maternelle 4 ans. Ce rapport présente les résultats provenant de l’évaluation du programme AE implanté dans 14 écoles montréalaises situées en milieux défavorisés. L'évaluation a cherché à mesurer les effets du programme sur les parents, les enfants et le milieu scolaire. En comparaison avec un groupe contrôle d’écoles, l’analyse des données recueillies ne permet pas de conclure à un effet du programme AE sur le développement socioaffectif et le développement cognitif des enfants ainsi que sur la qualité des interactions en classe de maternelle 4 ans. Certains effets du programme sont observés auprès des parents et des directions d'écoles. Toutefois, c'est principalement auprès des enseignantes que les effets de ce programme sont constatés. Les enseignantes rapportent des effets positifs sur les enfants, leur travail et les parents. Ces résultats contribuent à soutenir la réflexion sur la mise en place de pratiques de transition dans les milieux éducatifs

Évaluation du programme Accès à l’école : Analyse théorique et évaluation de l’implantation

Développé conjointement par des écoles et des centres de pédiatrie sociale, le programme Accès à l’école (AE) vise à soutenir l’enfant dans son expérience de la rentrée scolaire en maternelle 4 ans. Cet article présente des résultats provenant de l’évaluation de l'implantation de ce programme implanté dans 13 écoles montréalaises situées en milieux défavorisés. L’équipe de recherche a procédé à l’observation systématique de toutes les activités du programme. Également, des entrevues téléphoniques auprès des directions d’école, des enseignantes et de membres du personnel du service de garde en milieu scolaire ont été menées pour évaluer certains aspects du programme. \ud Les résultats font ressortir que le programme est implanté de manière conforme à son modèle théorique et uniforme dans l’ensemble des écoles. De manière générale, l’ensemble des milieux scolaires adhère fortement au programme et la plupart des directions d’école considère que le programme est facile à mettre en œuvre

Cognitive Restructuring for the Treatment of Gambling Related Thoughts: a Systematic Review

Cognitive restructuring is the best practice for treating gambling related thoughts, but some therapists do not apply this technique due to a lack of training regarding its application. The increase of skill game players (e.g., poker) entering treatment adds a challenge for therapists because these gamblers present with different thoughts than those of other gamblers usually encountered in treatment (e.g., EGM). This systematic review aims to describe how cognitive restructuring is carried out with gamblers, particularly skill game players, based on the evidence available in empirical studies that include cognitive interventions for gambling. Of the 2607 studies collected, 41 were retained. Results highlighted exposure as the most frequently used technique to facilitate identification of gambling related thoughts (imaginal = 19.5%; in vivo = 12.2% of studies). More than half of the studies (63.4%) clearly reported therapeutic techniques aimed at correcting gamblers’ thoughts, of which 30.8% involved visual support to challenge the thoughts (e.g. node link mapping, ABC log, cue-cards). Of the 41 retained studies, 46.3% included skill game players in their sample. However, 94.7% of these studies did not mention if cognitive restructuring had been adapted for these players. It was also observed that several terms referring to gamblers’ thoughts were used interchangeably (e.g. erroneous, dysfunctional, irrational or inadequate thoughts), although these terms could each refer to specific content. Clinical implications of the results are discussed with regards to the needs of therapists, but also in relation to editing constraints of scientific journals that may limit detailed description of cognitive restructuring procedures

The metabolic signature associated with the Western dietary pattern : a cross-sectional study

Background: Metabolic profiles have been shown to be associated to obesity status and insulin sensitivity. Dietary intakes influence metabolic pathways and therefore, different dietary patterns may relate to modifications in metabolic signatures. The objective was to verify associations between dietary patterns and metabolic profiles composed of amino acids (AAs) and acylcarnitines (ACs). Methods: 210 participants were recruited in the greater Quebec City area between September 2009 and December 2011. Dietary patterns had been previously derived using principal component analysis (PCA). The Prudent dietary pattern was characterised by higher intakes of vegetables, fruits, whole grain products, non-hydrogenated fat and lower intakes of refined grain products, whereas the Western dietary pattern was associated with higher intakes of refined grain products, desserts, sweets and processed meats. Targeted metabolites were quantified in 37 participants with the Biocrates Absolute IDQ p150 (Biocrates Life Sciences AG, Austria) mass spectrometry method (including 14 amino acids and 41 acylcarnitines). Results: PCA analysis with metabolites including AAs and ACs revealed two main components explaining the most variance in overall data (13.8%). PC1 was composed mostly of medium- to long-chain ACs (C16:2, C14:2, C14:2-OH, C16, C14:1-OH, C14:1, C10:2, C5-DC/C6-OH, C12, C18:2, C10, C4:1-DC/C6, C8:1 and C2) whereas PC2 included certain AAs and short-chain ACs (xLeu, Met, Arg, Phe, Pro, Orn, His, C0, C3, C4 and C5). The Western dietary pattern correlated negatively with PC1 and positively with PC2 (r = −0.34, p = 0.05 and r = 0.38, p = 0.03, respectively), independently of age, sex and BMI. Conclusion: These findings suggest that the Western dietary pattern is associated with a specific metabolite signature characterized by increased levels of AAs including branched-chain AAs (BCAAs) and short-chain ACs

An interaction effect between glucokinase gene variation and carbohydrate intakes modulates the plasma triglyceride response to a fish oil supplementation

A large inter-individual variability in the plasma triglyceride (TG) response to fish oil consumption has been observed. The objective was to investigate the gene-diet interaction effects between single-nucleotide polymorphisms (SNPs) within glucokinase (GCK) gene and dietary carbohydrate intakes (CHO) on the plasma TG response to a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a 6-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g EPA and 1.1 g DHA). Thirteen SNPs within GCK gene were genotyped using TAQMAN methodology. A gene-diet interaction effect on the plasma TG response was observed with rs741038 and CHO adjusted for age, sex and BMI (p = 0.008). In order to compare the plasma TG response between genotypes according to CHO, participants were divided according to median CHO. Homozygotes of the minor C allele of rs741038 with high CHO >48.59 % had a greater decrease in their plasma TG concentrations following the intake of fish oil (p < 0.05) than C/C homozygotes with low CHO and also than the other genotypes either with high or low CHO. The plasma TG response to a fish oil supplementation may be modulated by gene-diet interaction effects involving GCK gene and CHO

Genome-wide association study of dietary pattern scores

Dietary patterns, representing global food supplies rather than specific nutrients or food intakes, have been associated with cardiovascular disease (CVD) incidence and mortality. The contribution of genetic factors in the determination of food intakes, preferences and dietary patterns has been previously established. The current study aimed to identify novel genetic factors associated with reported dietary pattern scores. Reported dietary patterns scores were derived from reported dietary intakes for the preceding month and were obtained through a food frequency questionnaire and genome-wide association study (GWAS) conducted in a study sample of 141 individuals. Reported Prudent and Western dietary patterns demonstrated nominal associations (p < 1 × 10−5) with 78 and 27 single nucleotide polymorphisms (SNPs), respectively. Among these, SNPs annotated to genes previously associated with neurological disorders, CVD risk factors and obesity were identified. Further assessment of SNPs demonstrated an impact on gene expression levels in blood for SNPs located within/near BCKDHB (p = 0.02) and the hypothalamic glucosensor PFKFB3 (p = 0.0004) genes, potentially mediated through an impact on the binding of transcription factors (TFs). Overrepresentations of glucose/energy homeostasis and hormone response TFs were also observed from SNP-surrounding sequences. Results from the current GWAS study suggest an interplay of genes involved in the metabolic response to dietary patterns on obesity, glucose metabolism and food-induced response in the brain in the adoption of dietary patterns

Associations between dietary patterns and gene expression profiles of healthy men and women: a cross-sectional study

Background: Diet regulates gene expression profiles by several mechanisms. The objective of this study was to examine gene expression in relation with dietary patterns. Methods: Two hundred and fifty four participants from the greater Quebec City metropolitan area were recruited. Two hundred and ten participants completed the study protocol. Dietary patterns were derived from a food frequency questionnaire (FFQ) by factor analysis. For 30 participants (in fasting state), RNA was extracted from peripheral blood mononuclear cells (PBMCs) and expression levels of 47,231 mRNA transcripts were assessed using the Illumina Human-6 v3 Expression BeadChipsW. Microarray data was pre-processed with Flexarray software and analysed with Ingenuity Pathway Analysis (IPA). Results: Two dietary patterns were identified. The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats. When individuals with high scores for the Prudent dietary pattern where compared to individuals with low scores, 2,083 transcripts were differentially expressed in men, 1,136 transcripts in women and 59 transcripts were overlapping in men and women. For the Western dietary pattern, 1,021 transcripts were differentially expressed in men with high versus low scores, 1,163 transcripts in women and 23 transcripts were overlapping in men and women. IPA reveals that genes differentially expressed for both patterns were present in networks related to the immune and/or inflammatory response, cancer and cardiovascular diseases. Conclusion: Gene expression profiles were different according to dietary patterns, which probably modulate the risk of chronic diseases