Personne : Guénard, Frédéric
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Université Laval. Institut sur la nutrition et les aliments fonctionnels
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- PublicationAccès libreGenome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid (PUFA) supplementation.(jlr.org, 2014-05-19) Guénard, Frédéric; Rudkowska, Iwona; Barbier, Olivier; Lemieux, Simone; Julien, Pierre; Vohl, Marie-Claude; Calder, Philip C.; Couture, Patrick; Minihane, Anne MarieStudies have shown a large interindividual variability in plasma TG response to long-chain n-3 PUFA supplementation, which may likely be attributable to genetic variability within the populations studied. The objective is to compare the frequency of SNPs in a genome-wide association study between responders (reduction in plasma TG levels ≥0.01 mM) and nonresponders (increase in plasma TG of ≥0 mM) to supplementation. Genomic DNA from 141 subjects who completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil daily (1.9-2.2 g EPA and 1.1 g DHA daily) were genotyped on Illumina HumanOmni-5-QuadBeadChip. Thirteen loci had frequency differences between responders and nonresponders (P < 1 × 10(-5)), including SNPs in or near IQCJ-SCHIP1, MYB, NELL1, NXPH1, PHF17, and SLIT2 genes. A genetic risk score (GRS) was constructed by summing the number of risk alleles. This GRS explained 21.53% of the variation in TG response to n-3 PUFA supplementation when adjusted for age, sex, and BMI (P = 0.0002). Using Fish Oil Intervention and Genotype as a replication cohort, the GRS was able to explain 2% of variation in TG response when adjusted. In conclusion, subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profile than individuals who do not respond.
- PublicationAccès libreEffect of different concentrations of omega-3 fatty acids on stimulated THP-1 macrophages(Springer-Verlag, 2017-02-21) Guénard, Frédéric; Allam-Ndoul, Bénédicte; Barbier, Olivier; Vohl, Marie-ClaudeBackground: Inflammation plays a central role in chronic diseases occurring in the contemporary society. The health benefits of omega-3 (n-3) fatty acids (FAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been reported. However, their mechanisms of action are poorly understood. We explored dose and time effects of EPA, DHA, and a mixture of EPA + DHA on the expression of inflammatory genes in stimulated macrophages. Methods: Lipopolysaccharide was used to stimulate human THP-1 macrophages. Cells were incubated in different conditions in the presence of n-3 FAs and LPS, and mRNA levels of inflammatory genes were measured by real-time PCR. Cytokine levels in culture media were measured. Results: The mixture of EPA + DHA had a more effective inhibitory effect than either DHA or EPA alone, DHA being more potent than EPA. For both EPA and DHA, 75 μM of FAs had a more important anti-inflammatory effect than 10 or 50 μM. For gene expression, EPA had the greater action during the post-incubation (after LPS treatment) condition while DHA and EPA + DHA were more potent during the co-incubation (n-3 FAs and LPS). Cytokine concentrations decreased more markedly in the co-incubation condition. Conclusions: These results suggest that in stimulated macrophages, expression levels of genes involved in inflammation are influenced by the dose, the type of n-3 FAs, and the time of incubation.
- PublicationAccès libreA study of the differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on gene expression profiles of stimulated Thp-1 macrophages(MDPI, 2017-01-23) Guénard, Frédéric; Allam-Ndoul, Bénédicte; Barbier, Olivier; Vohl, Marie-ClaudeBackground: An appropriate intake of omega-3 (n-3) fatty acids (FAs) such as eicosapentaenoic and docosahexaenoic acid (EPA/DHA) from marine sources is known to have anti-inflammatory effects. However, molecular mechanisms underlying their beneficial effects on health are not fully understood. The aim of the present study was to characterize gene expression profiles of THP-1 macrophages, incubated in either EPA or DHA and stimulated with lipopolysaccharide (LPS), a pro-inflammatory agent. Methods: THP-1 macrophages were incubated into 10, 50 and 75 µM of EPA or DHA for 24 h, and 100 nM of LPS was added to the culture media for 18 h. Total mRNA was extracted and gene expression examined by microarray analysis using Illumina Human HT-12 expression beadchips (Illumina). Results: Pathway analysis revealed that EPA and DHA regulate genes involved in cell cycle regulation, apoptosis, immune response and inflammation, oxidative stress and cancer pathways in a differential and dose-dependent manner. Conclusions: EPA and DHA appear to exert differential effects on gene expression in THP-1 macrophages. Specific effects of n-3 FAs on gene expression levels are also dose-dependent.
- PublicationAccès libreGenetic risk score predictive of the plasma triglyceride response to an Omega-3 fatty acid supplementation in a mexican population(MDPI, 2019-03-29) Guénard, Frédéric; Vallée-Marcotte, Bastien; Marquis, Julien; Vohl, Marie-Claude; Charpagne, Aline; Vadillo-Ortega, Felipe; Tejero, Maria Elizabeth; Binia, AristeaOur group built a genetic risk score (GRS) of the plasma triglyceride (TG) response to an omega-3 (n-3) fatty acid (FA) supplementation in Caucasian Canadians that explained 21.53% of the TG variance. The objective was to refine the GRS by fine mapping and to test its association with the TG response in young Mexican adults. A total of 191 participants underwent a 6-week n-3 FA supplementation providing 2.7g/day of docosahexaenoic and eicosapentaenoic acids. Using quantitative polymerase chain reaction (PCR), 103 single-nucleotide polymorphisms (SNPs) were genotyped. A stepwise regression adjusted for age, sex, and body mass index (BMI) was used to select the strongest SNPs to include in the genetic risk model. A GRS was calculated from the sum of at-risk alleles. The contribution of the GRS to the TG response was assessed by ANCOVA with age, sex, and BMI included in the model. Several differences in allele frequency were observed between Canadians and Mexicans. Five lead SNPs were included in the genetic risk model, in which the GRS accounted for 11.01% of the variance of the TG response (p < 0.0001). These findings highlight the important contribution of genetic factors to the heterogeneity of the TG response to an n-3 FA supplementation among Mexicans.
- PublicationAccès librePlasma triglyceride levels may be modulated by gene expression of IQCJ, NXPH1, PHF17 and MYB in humans(M D P I AG, 2017-01-26) Guénard, Frédéric; Vallée-Marcotte, Bastien; Cormier, Hubert; Rudkowska, Iwona; Lemieux, Simone; Vohl, Marie-Claude; Couture, PatrickA genome-wide association study (GWAS) by our group identified loci associated with the plasma triglyceride (TG) response to ω-3 fatty acid (FA) supplementation in IQCJ, NXPH1, PHF17 and MYB. Our aim is to investigate potential mechanisms underlying the associations between single nucleotide polymorphisms (SNPs) in the four genes and TG levels following ω-3 FA supplementation. 208 subjects received 3 g/day of ω-3 FA (1.9–2.2 g of EPA and 1.1 g of docosahexaenoic acid (DHA)) for six weeks. Plasma TG were measured before and after the intervention. 67 SNPs were selected to increase the density of markers near GWAS hits. Genome-wide expression and methylation analyses were conducted on respectively 30 and 35 participants’ blood sample together with in silico analyses. Two SNPs of IQCJ showed different affinities to splice sites depending on alleles. Expression levels were influenced by genotype for one SNP in NXPH1 and one in MYB. Associations between 12 tagged SNPs of IQCJ, 26 of NXPH1, seven of PHF17 and four of MYB and gene-specific CpG site methylation levels were found. The response of plasma TG to ω-3 FA supplementation may be modulated by the effect of DNA methylation on expression levels of genes revealed by GWAS.
- PublicationAccès libreNovel genetic loci associated with the plasma triglyceride response to an omega-3 fatty acid supplementation(Karger, 2016-06-01) Vallée-Marcotte, Bastien; Cormier, Hubert; Guénard, Frédéric; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-ClaudeA recent genome-wide association study (GWAS) by our group identified 13 loci associated with the plasma triglyceride (TG) response to omega-3 (n-3) fatty acid (FA) supplementation. This study aimed to test whether single-nucleotide polymorphisms (SNPs) within the IQCJ, NXPH1, PHF17 and MYB genes are associated with the plasma TG response to an n-3 FA supplementation. Methods: A total of 208 subjects followed a 6-week n-3 FA supplementation of 5 g/day of fish oil (1.9-2.2 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Measurements of plasma lipids were made before and after the supplementation. Sixty-seven tagged SNPs were selected to increase the density of markers near GWAS hits. Results: In a repeated model, independent effects of the genotype and the gene-supplementation interaction were associated with plasma TG. Genotype effects were observed with two SNPs of NXPH1, and gene-diet interactions were observed with ten SNPs of IQCJ, four SNPs of NXPH1 and three SNPs of MYB. Positive and negative responders showed different genotype frequencies with nine SNPs of IQCJ, two SNPs of NXPH1 and two SNPs of MYB. Conclusion: Fine mapping in GWAS-associated loci allowed the identification of SNPs partly explaining the large interindividual variability observed in plasma TG levels in response to an n-3 FA supplementation.
- PublicationAccès libreEpigenetic changes in blood leukocytes following an omega-3 fatty acid supplementation(BiomedCentral, 2017-04-26) Guénard, Frédéric; Rudkowska, Iwona; Lemieux, Simone; Tremblay, Bénédicte L.; Vohl, Marie-Claude; Couture, PatrickBackground: Omega-3 polyunsaturated fatty acids (n-3 FAs) have several beneficial effects on cardiovascular (CV) disease risk factors. These effects on CV risk profile may be mediated by several factors, including epigenetic modifications. Our objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in overweight and obese subjects and to identify specific biological pathways potentially altered by the supplementation. Results: Blood leukocytes genome-wide DNA methylation profiles of 36 overweight and obese subjects before and after a 6-week supplementation with 3 g of n-3 FAs were compared using GenomeStudio software. After supplementation, 308 CpG sites, assigned to 231 genes, were differentially methylated (FDR-corrected Diffscore ≥│13│~ P ≤ 0.05). Using Ingenuity Pathway Analysis system, a total of 55 pathways were significantly overrepresented following supplementation. Among these pathways, 16 were related to inflammatory and immune response, lipid metabolism, type 2 diabetes, and cardiovascular signaling. Changes in methylation levels of CpG sites within AKT3, ATF1, HDAC4, and IGFBP5 were correlated with changes in plasma triglyceride and glucose levels as well as with changes in the ratio of total cholesterol/HDL-cholesterol following the supplementation. Conclusions: These data provide key differences in blood leukocytes DNA methylation profiles of subjects following an n-3 FA supplementation, which brings new, potential insights on metabolic pathways underlying the effects of n-3 FAs on CV health.
- PublicationAccès librePrevention of potential adverse metabolic effects of a supplementation with omega-3 fatty acids using a genetic score approach(Karger, 2019-11-29) Franck, Maximilien; Guénard, Frédéric; Toro Martin, Juan de; Rudkowska, Iwona; Lamarche, Benoît; Lemieux, Simone; Vohl, Marie-Claude; Couture, PatrickIntroduction: The consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to have beneficial health effects, notably, by reducing plasma triglyceride levels. Nonetheless, a concomitant decrease in insulin sensitivity has also been observed, but is highly variable among subjects. Herein, we aimed to determine the importance of the genetic background in the interindividual variability of the insulin sensitivity response following an n-3 PUFA supplementation. Methods: A total of 210 participants completed a 6-week n-3 PUFA supplementation with 5 g/day of fish oil (providing 1.9–2.2 g of eicosapentaenoic acid + 1.1 g of docosahexaenoic acid). Insulin resistance was estimated by the homeostatic model assessment (HOMA-IR), and participants were further classified as high-risk or low-risk depending on their HOMA-IR change following the n-3 PUFA supplementation, as compared to pre-supplementation values. Genome-wide genotyping data were obtained for 138 participants using HumanOmni-5-Quad BeadChips containing 4,301,331 single nucleotide polymorphisms. A genome-wide association analysis (GWAS) was carried out between high-risk and low-risk participants. The population study was split into training (60%) and testing (40%) datasets to assess the predictive accuracy of a genetic risk score (GRS) constructed by summing the number of risk alleles. Results: Following the n-3 PUFA supplementation, 32 participants had increased HOMA-IR as compared to initial values and were classified as high risk (23.2%), whereas remaining subjects were classified as low risk (n = 106, 76.8%). A total of 8 loci had frequency differences between high-risk and low-risk participants at a suggestive GWAS association threshold (p value <1 × 10–5). After applying 10-fold cross validation, the GRS showed a significant association with the risk of increased HOMA-IR in the testing dataset (OR = 3.16 [95% CI, 1.85–7.14]), with a predictive accuracy of 0.85, and explained 40% of variation in HOMA-IR change. Conclusions: These results suggest that the genetic background has a relevant role in the interindividual variability observed in the insulin sensitivity response following an n-3 PUFA supplementation. Subjects being at risk of insulin sensitivity lowering following an n-3 PUFA supplementation may be identified using genetic-based precision nutrition approaches
- PublicationAccès libreGenetic risk prediction of the plasma triglyceride response to independent supplementations with eicosapentaenoic and docosahexaenoic acids : the 2 ComparED study(BioMed Central Ltd., 2020-06-15) Guénard, Frédéric; Vallée-Marcotte, Bastien; Toro Martin, Juan de; Lamarche, Benoît; Allaire, Janie; Vohl, Marie-Claude; Couture, PatrickBackground : We previously built a genetic risk score (GRS) highly predictive of the plasma triglyceride (TG) response to an omega-3 fatty acid (n-3 FA) supplementation from marine sources. The objective of the present study was to test the potential of this GRS to predict the plasma TG responsiveness to supplementation with either eicosapentaenoic (EPA) or docosahexaenoic (DHA) acids in the Comparing EPA to DHA (ComparED) Study. Methods : The ComparED Study is a double-blind, controlled, crossover trial, with participants randomized to three supplemented phases of 10 weeks each: (1) 2.7 g/day of DHA, (2) 2.7 g/day of EPA, and (3) 3 g/day of corn oil (control), separated by 9-week washouts. The 31 SNPs used to build the previous GRS were genotyped in 122 participants of the ComparED Study using TaqMan technology. The GRS for each participant was computed by summing the number of rare alleles. Ordinal and binary logistic models, adjusted for age, sex, and body mass index, were used to calculate the ability of the GRS to predict TG responsiveness. Results : The GRS predicted TG responsiveness to EPA supplementation (p = 0.006), and a trend was observed for DHA supplementation (p = 0.08). The exclusion of participants with neutral TG responsiveness clarified the association patterns and the predictive capability of the GRS (EPA, p = 0.0003, DHA p = 0.01). Conclusion : Results of the present study suggest that the constructed GRS is a good predictor of the plasma TG response to supplementation with either DHA or EPA.