Background Using a genome-wide association study (GWAS) approach, our group previously computed a genetic risk score (GRS) from single nucleotide polymorphisms (SNPs) of 10 loci that affect the plasma triglyceride (TG) response to an omega-3 (n–3) fatty acid (FA) supplementation. Objectives The objective was to compute a novel and more refined GRS using fine mapping to include a large number of genetic variants. Methods A total of 208 participants of the Fatty Acid Sensor (FAS) Study received 5 g fish oil/d, containing 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexanoic acid, for 6 wk. Plasma TG concentrations were measured before and after supplementation. Dense genotyping and genotype imputation were used to refine mapping around GWAS hits. A GRS was computed by summing the number of at-risk alleles of tagging SNPs. Analyses were replicated in samples of the FINGEN study. Results A total of 31 tagging SNPs associated with the TG response were used for GRS calculation in the FAS study. In a general linear model adjusted for age, sex, and body mass index, the GRS explained 49.73% of TG response variance (P < 0.0001). Nonresponders to the n–3 FA supplementation had a higher GRS than did responders. In the FINGEN replication study, the GRS explained 3.67% of TG response variance (P = 0.0006). Conclusions Fine mapping proved to be effective to refine the previous GRS. Carrying increasing numbers of at-risk alleles of 31 SNPs confers a higher risk of being nonresponsive to n–3 FAs. The genetic profile therefore appears to be an important determinant of the plasma TG response to an n–3 FA supplementation and could be used to target those most likely to gain clinical benefit. This trial was registered at http://www.clinicaltrials.gov as NCT01343342.
Although numerous studies have reported the benefits of apple consumption on cardiometabolic health parameters and chronic disease prevention, few have focused on the effects of apple juice specifically. Juice consumption may be a convenient way to take advantage of the health effects of the bioactive components present in apples. The present review aims to summarize the current literature on health benefits of apple juice as reported in clinical trials in humans. Of the 67 studies retained, 20 interventional studies on humans were reviewed. Overall, cloudy apple juice consumption was found to be associated with several markers of cardiovascular health that may ultimately be relevant for cancer and neurodegenerative diseases. Most of the documentation was found regarding oxidative stress, as well as observations with other parameters such as markers of inflammation, lipid profile, and diabetes. This review suggests that, in 20 studies, apple juice consumed in moderation exerts positive effects on markers of cardiovascular disease risk (particularly on oxidative stress).
Background: 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. Trial registration: ClinicalTrials.gov, NCT01810003. The study protocol was registered on March 4, 2013.
A 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.
Objective The purpose of this study was to draw a global portrait of the current knowledge and interest regarding nutrigenetics in a population of French Canadians from the province of Quebec (Canada). Methods A total of 2238 residents from the province of Quebec, Canada, were recruited via social networks and from the Laval University employee/student lists to participate in a 37-question online survey on nutrigenetics. Results Most participants were not familiar with the term “nutrigenetics” (82.7%). Participants with good genetic literacy (26.8%) were less interested in nutrigenetic testing ( p < 0.0001). The vast majority of participants (90.7%) reported to be willing to follow a personalised diet based on nutrigenetic testing, especially if they came to know themselves as carriers of a polymorphism increasing the risk of certain diseases. Participants had a higher interest in testing related to metabolic response to macronutrients (types of sugars, fats and proteins) than to micronutrients or other nutrients related to food intolerance. Conclusions The attitude of French Canadians about nutrigenetics is very consistent with the results from other surveys published in the literature. Although few individuals are familiar with nutrigenetics, the public’s attitude towards nutrigenetics is globally favourable. Electronic supplementary material The online version of this article (10.1186/s12263-019-0629-7) contains supplementary material, which is available to authorized users.
Background Supplementation with long chain n‐3 polyunsaturated fatty acids is used to reduce total circulating triacylglycerol (TAG) concentrations. However, in about 30% of people, supplementation with long chain n‐3 polyunsaturated fatty acids does not result in decreased plasma TAG. Lipidomic analysis may provide insight into this inter‐individual variability. Methods Lipidomic analyses using targeted, mass spectrometry were performed on plasma samples obtained from a clinical study in which participants were supplemented with 3 g/day of long chain n‐3 in the form of fish oil capsules over a 6‐week period. TAG species and cholesteryl esters (CE) were quantified for 130 participants pre‐ and post‐supplementation. Participants were segregated into 3 potential responder phenotypes: (1) positive responder (R pos ; TAG decrease), (2) non‐responder (R non ; lacking TAG change), and (3) negative responder (R neg ; TAG increase) representing 67%, 18%, and 15% of the study participants, respectively. Separation of the 3 phenotypes was attributed to differential responses in TAG with 50 to 54 carbons with 1 to 4 desaturations. Elevated TAG with higher carbon number and desaturation were common to all phenotypes following supplementation. Using the TAG responder phenotype for grouping, decreases in total CE and specific CE occurred in the R pos phenotype versus the R neg phenotype with intermediate responses in the R non phenotype. CE 20:5, containing eicosapentaenoic acid (20:5n‐3), was elevated in all phenotypes. A classifier combining lipidomic and genomic features was built to discriminate triacylglycerol response phenotypes and reached a high predictive performance with a balanced accuracy of 75%. Conclusions These data identify lipidomic signatures, TAG and CE, associated with long chain n‐3 response p henotypes and identify a novel phenotype based upon CE changes. Registration URL: https://www.ClinicalTrials.gov ; Unique Identifier: NCT01343342.
The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs) are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3) fatty acids (FA) (1.9–2.2 g of eicosapentaenoic acid (EPA) and 1.1 g of docosahexaenoic acid (DHA)) during six weeks. Biochemical parameters were taken before and after the supplementation. Using the HapMap database and the tagger procedure in Haploview, 12 tagging SNPs in FFAR4 were selected and then genotyped using TaqMan technology. Transcript expression levels were measured for 30 participants in peripheral mononuclear blood cells. DNA methylation levels were measured for 35 participants in leukocytes. In silico analyses were also performed. Four gene–diet interactions on fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) index values were found. rs17108973 explained a significant proportion of the variance of insulin levels (3.0%) and HOMA-IR (2.03%) index values. Splice site prediction was different depending on the allele for rs11187527. rs17108973 and rs17484310 had different affinity for transcription factors depending on the allele. n-3 FAs effectively improve insulin-related traits for major allele homozygotes of four FFAR4 SNPs as opposed to carriers of the minor alleles.
Our 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.
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