Dataset Information

Genetic Risk Score Predictive of the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation in a Mexican Population.

ABSTRACT: 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.

SUBMITTER: Vallee Marcotte B

PROVIDER: S-EPMC6521301 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Genetic Risk Score Predictive of the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation in a Mexican Population.

Vallée Marcotte Bastien B Guénard Frédéric F Marquis Julien J Charpagne Aline A Vadillo-Ortega Felipe F Tejero Maria Elizabeth ME Binia Aristea A Vohl Marie-Claude MC

Nutrients 20190329 4

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 r ...[more]

PMID: 30934900

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Project description:The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2, and 4 portions of oily fish per week for 12 months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE*n-3 PUFA dose effect was observed for the CYP-ω hydroxylase products 19-HEPE (p = 0.027) and 20-HEPE (p = 0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p = 0.014). Low basal plasma EPA levels (EPA < 0.85% of total fatty acids) were associated with a greater change in 5-HEPE, 9-HEPE, 11-HEPE, and 20-HEPE compared to high basal EPA levels (EPA > 1.22% of total fatty acids). In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for 12 months.

Project description:ObjectiveTo examine fatty acid profiles, their response to omega-3 fatty acid (Ω3) supplementation, and associations with clinical status and treatment response in youth with mood disorders.MethodsIn a placebo-controlled 2X2 design, 7-14 year-olds (N = 95) in parallel pilot trials (depression N = 72; bipolar N = 23) were randomly assigned to 12 weeks of Ω3 supplementation (1.4 g eicosapentaenoic acid [EPA], 0.2 g docosahexaenoic acid [DHA], and 0.27 g other Ω3 per day); psychoeducational psychotherapy (PEP); their combination; or placebo (mainly oleic and linoleic acid) alone. Blood was drawn at baseline (N = 90) and endpoint (n = 65). Fatty acid levels were expressed as percent of total plasma fatty acids. Correlational and moderator/mediator analyses were done with SPSS Statistics 23.ResultsAt baseline: (1) DHA correlated negatively with alpha-linolenic acid (ALA) (r = -0.23, p = 0.029); (2) Arachidonic acid (AA, Ω6) correlated negatively with global functioning (r = -0.24, p = 0.022); (3) Total Ω3 correlated negatively with age (r = -0.22, p = 0.036) and diastolic blood pressure (r = -0.31, p = 0.006). Moderation: Baseline ALA moderated response to Ω3 supplementation: ALA levels above the sample mean (lower DHA) predicted significantly better placebo-controlled response (p = 0.04). Supplementation effects: Compared to placebo, 2 g Ω3 per day increased EPA blood levels sevenfold and DHA levels by half (both p < 0.001). Body weight correlated inversely with increased EPA (r = -0.52, p = 0.004) and DHA (r = -0.54, p = 0.003) and positively with clinical mood response. Mediation: EPA increase baseline-to-endpoint mediated placebo-controlled global function and depression improvement: the greater the EPA increase, the less the placebo-controlled Ω3 improvement.ConclusionΩ3 supplementation at 2 g/day increases blood levels substantially, more so in smaller children. A possible U-shaped response curve should be explored.

Project description:BACKGROUND:Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50% of brain dry weight). Total brain lipids is constituted of more than 60% of phospholipids, in which docosahexaenoic acid (DHA, 22:6n-3) is the most abundant (more than 40%) polyunsaturated fatty acid (PUFA) in brain membrane phospholipids. Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA in peripheral blood (plasma and erythrocyte membranes) as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary omega-3 fatty acid supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population. METHODS:In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. The rationale why omega-3 supplementation was beneficial on symptoms (presented by subscales of the positive and negative symptom scale (PANSS), and cognitive functions in certain patients but not others was reviewed. The potential mechanisms underlying the beneficial effects were discussed. RESULTS:Omega-3 fatty acid supplementation reduced the conversion rate to psychosis and improved both positive and negative symptoms and global functions in adolescents at ultra-high risk for psychosis. Omega-3 fatty acid supplementation could also improve negative symptoms and global functions in the first-episode patients with schizophrenia, but improve mainly total or general PANSS subscales in chronic patients. Patients with low PUFA (particularly DHA) baseline in blood were more responsive to the omega-3 fatty acid intervention. CONCLUSION:Omega-3 supplementation is more effective in reducing psychotic symptom severity in young adults or adolescents in the prodromal phase of schizophrenia who have low omega-3 baseline. Omega-3 supplementation was more effective in patients with low PUFA baseline. It suggests that patients with predefined lipid levels might benefit from lipid treatments, but more controlled clinical trials are warranted.

Dataset Information

Genetic Risk Score Predictive of the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation in a Mexican Population.

Publications

Genetic Risk Score Predictive of the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation in a Mexican Population.

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