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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.
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Regulação da Expressão Gênica , Glicoproteínas/genética , Proteínas de Homeodomínio/genética , Neuropeptídeos/genética , Proteínas Proto-Oncogênicas c-myc/genética , Triglicerídeos/sangue , Proteínas Supressoras de Tumor/genética , Adulto , Metilação de DNA/genética , Estudo de Associação Genômica Ampla , Glicoproteínas/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Neuropeptídeos/metabolismo , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
PURPOSE: To examine whether yogurt consumption is associated with a healthier dietary pattern and with a better cardio-metabolic risk profile among healthy individuals classified on the basis of their body mass index (BMI). METHODS: A 91-item food frequency questionnaire, including data on yogurt consumption, was administered to 664 subjects from the INFOGENE study. After principal component analysis, two factors were retained, thus classified as the Prudent and Western dietary patterns. RESULTS: Yogurt was a significant contributor to the Prudent dietary pattern. Moreover, yogurt consumption was associated with lower body weight, waist-to-hip ratio, and waist circumference and tended to be associated with a lower BMI. Consumers had lower levels of fasting total cholesterol and insulin. Consumers of yogurt had a positive Prudent dietary pattern mean score, while the opposite trend was observed in non-consumers of yogurt. Overweight/obese individuals who were consumers of yogurts exhibited a more favorable cardio-metabolic profile characterized by lower plasma triglyceride and insulin levels than non-consumers within the same range of BMI. There was no difference in total yogurt consumption between normal-weight individuals and overweight/obese individuals. However, normal-weight subjects had more daily servings of high-fat yogurt and less daily servings of fat-free yogurt compared to overweight/obese individuals. CONCLUSIONS: Being a significant contributor to the Prudent dietary pattern, yogurt consumption may be associated with healthy eating. Also, yogurt consumption may be associated with lower anthropometric indicators and a more beneficial cardio-metabolic risk profile in overweight/obese individuals.
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Doenças Cardiovasculares/epidemiologia , Dieta , Síndrome Metabólica/epidemiologia , Iogurte , Adolescente , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Insulina/sangue , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Sobrepeso/sangue , Sobrepeso/epidemiologia , Análise de Componente Principal , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Triglicerídeos/sangue , Circunferência da Cintura , Relação Cintura-Quadril , Adulto JovemRESUMO
(1) BACKGROUND: A growing body of literature suggest that polymorphisms (SNPs) from inflammation-related genes could possibly play a role in cytokine production and then interact with dietary n-3 fatty acids (FAs) to modulate inflammation. The aim of the present study was to test whether gene expression of selected inflammatory genes was altered following an n-3 PUFA supplementation and to test for gene-diet interactions modulating plasma inflammatory biomarker levels. (2) METHODS: 191 subjects completed a 6-week n-3 FA supplementation with 5 g/day of fish oil. Gene expression of TNF-α and IL6 was assessed in peripheral blood mononuclear cells (PBMCs) using the TaqMan technology. Genotyping of 20 SNPs from the TNF-LTA gene cluster, IL1ß, IL6 and CRP genes was performed. (3) RESULTS: There was no significant reduction of plasma IL-6, TNF-α and C-reactive protein (CRP) levels after the 6-week fish oil supplementation. TNF-α and IL6 were slightly overexpressed in PBMCs after the supplementation (fold changes of 1.05 ± 0.38 and 1.18 ± 0.49, respectively (n = 191)), but relative quantification (RQ) within the -0.5 to 2.0 fold are considered as nonbiologically significant. In a MIXED model for repeated measures adjusted for the effects of age, sex and BMI, gene by supplementation interaction effects were observed for rs1143627, rs16944, rs1800797, and rs2069840 on IL6 levels, for rs2229094 on TNF-α levels and for rs1800629 on CRP levels (p < 0.05 for all). (4) CONCLUSIONS: This study shows that a 6-week n-3 FA supplementation with 5 g/day of fish oil did not alter gene expression levels of TNF-α and IL6 in PBMCs and did not have an impact on inflammatory biomarker levels. However, gene-diet interactions were observed between SNPs within inflammation-related genes modulating plasma inflammatory biomarker levels.
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Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Inflamação/metabolismo , Interleucina-6/genética , Receptores Imunológicos/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Óleos de Peixe/química , Expressão Gênica , Interação Gene-Ambiente , Humanos , Inflamação/sangue , Inflamação/dietoterapia , Interleucina-6/sangue , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/sangue , Receptores Imunológicos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Fish oil-derived long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma triglyceride (TG) levels. Genetic factors such as single-nucleotide polymorphisms (SNPs) found in genes involved in metabolic pathways of n-3 PUFA could be responsible for well-recognized heterogeneity in plasma TG response to n-3 PUFA supplementation. Previous studies have shown that genes in the glycerophospholipid metabolism such as phospholipase A2 (PLA2) group II, IV, and VI, demonstrate changes in their expression levels in peripheral blood mononuclear cells (PBMCs) after n-3 PUFA supplementation. METHODS: A total of 208 subjects consumed 3 g/day of n-3 PUFA for 6 weeks. Plasma lipids were measured before and after the supplementation period. Five SNPs in PLA2G2A, six in PLA2G2C, eight in PLA2G2D, six in PLA2G2F, 22 in PLA2G4A, five in PLA2G6, and nine in PLA2G7 were genotyped. The MIXED Procedure for repeated measures adjusted for age, sex, BMI, and energy intake was used in order to test whether the genotype, supplementation or interaction (genotype by supplementation) were associated with plasma TG levels. RESULTS: The n-3 PUFA supplementation had an independent effect on plasma TG levels. Genotype effects on plasma TG levels were observed for rs2301475 in PLA2G2C, rs818571 in PLA2G2F, and rs1569480 in PLA2G4A. Genotype x supplementation interaction effects on plasma TG levels were observed for rs1805018 in PLA2G7 as well as for rs10752979, rs10737277, rs7540602, and rs3820185 in PLA2G4A. CONCLUSION: These results suggest that, SNPs in PLA2 genes may influence plasma TG levels during a supplementation with n-3 PUFA. This trial was registered at clinicaltrials.gov as NCT01343342.
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Ácidos Graxos Ômega-3/uso terapêutico , Fosfolipases A2/genética , Polimorfismo de Nucleotídeo Único/genética , Triglicerídeos/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Adulto , Suplementos Nutricionais , Feminino , Estudos de Associação Genética , Fosfolipases A2 do Grupo II/genética , Fosfolipases A2 do Grupo VI/genética , Humanos , MasculinoRESUMO
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.
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BACKGROUND/AIMS: This study aimed to evaluate attitudes, perceptions, and concerns about nutrigenetic testing for personalized nutrition in the general population of the province of Quebec in Canada. METHODS: A total of 1,425 individuals from the province of Quebec completed a 37-question online survey on nutrigenetics and were included in analyses. The χ2 test was used to test for associations between categorical variables. RESULTS: The majority of the participants (93.3%) considered dietitians the best professionals to give personalized dietary advice based on nutrigenetic testing. The main reported advantage for nutrigenetic testing was "health" (23.5%), followed by "disease prevention" (22.2%). Among the disadvantages, "no disadvantage" (24.4%), followed by "diet restriction" (12.9%) were mostly reported. The 2 major concerns raised were accessibility to genetic testing by telemarketing companies and spammers (51.8%), and solicitation by companies using personal genetic data to sell products (48.6%). CONCLUSIONS: French Canadians generally have a positive attitude towards nutrigenetics and consider its use to have many benefits. They expressed concern about possible confidentiality issues associated with the management or property of genetic test results. Education about such issues is needed. Overall, our findings suggest that the population is interested in more extensive use of nutrigenetics in health management.
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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.
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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.
Assuntos
Doenças Cardiovasculares/complicações , Hiperlipidemias/complicações , Síndrome Metabólica/complicações , Obesidade/complicações , Sobrepeso/complicações , Adulto , Aminoácidos/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Carnitina/análogos & derivados , Carnitina/sangue , Colesterol/sangue , HDL-Colesterol/sangue , Feminino , Glicerofosfolipídeos/sangue , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Sobrepeso/sangue , Sobrepeso/metabolismo , Análise de Componente Principal , Quebeque/epidemiologia , Fatores de Risco , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
BACKGROUND: A 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.
Assuntos
Proteínas de Ligação a Calmodulina/genética , Ácidos Graxos Ômega-3/administração & dosagem , Genes myb , Glicoproteínas/genética , Proteínas de Homeodomínio/genética , Neuropeptídeos/genética , Triglicerídeos/sangue , Proteínas Supressoras de Tumor/genética , Adulto , Suplementos Nutricionais , Feminino , Óleos de Peixe/administração & dosagem , Estudo de Associação Genômica Ampla , Humanos , Masculino , Nutrigenômica , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Polymorphisms (SNPs) within the FADS gene cluster and the ELOVL gene family are believed to influence enzyme activities after an omega-3 (n-3) fatty acid (FA) supplementation. The objectives of the study are to test whether an n-3 supplementation is associated with indexes of desaturase and elongase activities in addition to verify whether SNPs in the FADS gene cluster and the ELOVL gene family modulate enzyme activities of desaturases and elongases. A total 208 subjects completed a 6-week supplementation period with 5 g/day of fish oil (1.9-2.2 g/day of EPA + 1.1 g/day of DHA). FA profiles of plasma phospholipids were obtained by gas chromatography (n = 210). Desaturase and elongase indexes were estimated using product-to-precursor ratios. Twenty-eight SNPs from FADS1, FADS2, FADS3, ELOVL2 and ELOVL5 were genotyped using TaqMan technology. Desaturase indexes were significantly different after the 6-week n-3 supplementation. The index of δ-5 desaturase activity increased by 25.7 ± 28.8 % (p < 0.0001), whereas the index of δ-6 desaturase activity decreased by 17.7 ± 18.2 % (p < 0.0001) post-supplementation. Index of elongase activity decreased by 39.5 ± 27.9 % (p < 0.0001). Some gene-diet interactions potentially modulating the enzyme activities of desaturases and elongases involved in the FA metabolism post-supplementation were found. SNPs within the FADS gene cluster and the ELOVL gene family may play an important role in the enzyme activity of desaturases and elongases, suggesting that an n-3 FAs supplementation may affect PUFA metabolism.
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UNLABELLED: Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. OBJECTIVE: To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. METHODS: 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g-2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. RESULTS: Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). CONCLUSION: RESULTS suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation.
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BACKGROUND: Marine omega-3 (n-3) polyunsaturated fatty acids (PUFA) reduce plasma triglyceride (TG) levels. Genetic factors such as single nucleotide polymorphisms (SNPs) could be responsible for the variability of the plasma TG response to n-3 PUFA supplementation. Previous studies have demonstrated that n-3 PUFA supplementation using fish oil modified the expression levels of three genes involved in the TG synthesis pathway (GPAM, AGPAT3 and AGPAT4) in peripheral blood mononuclear cells. METHODS: A total of 210 subjects consumed 5 g/day of a fish oil supplement for 6 weeks. Plasma lipids were measured before and after the supplementation period. Three SNPs in GPAM, 13 SNPs in AGPAT3 and 35 SNPs in AGPAT4 were genotyped. RESULTS: In an ANOVA for repeated measures adjusted for age, sex and BMI, genotype effects on plasma TG levels were observed for rs1838452 in AGPAT3 as well as for rs746731 and rs2293286 in AGPAT4. Genotype × supplementation interaction effects on plasma TG levels were observed for rs2792751 and rs17129561 in GPAM as well as for rs3798943 and rs9458172 in AGPAT4 (p < 0.05). CONCLUSION: These results suggest that SNPs in genes involved in the TG synthesis pathway may influence plasma TG levels after n-3 PUFA supplementation.
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Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Metabolismo dos Lipídeos/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos/biossíntese , Triglicerídeos/sangue , Adolescente , Adulto , Suplementos Nutricionais , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: To test whether age, sex, body mass index (BMI), and the apolipoprotein E (APOE) genotype are associated with the metabolic response to an n-3 polyunsaturated fatty acid (PUFA) supplementation. METHODS: 210 subjects followed a 2-week run-in period based on Canada's Food Guide and underwent a 6-week 5 g/day fish oil supplementation (1.9 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Cardiovascular disease risk factors were measured. RESULTS: n-3 PUFA supplementation was associated with a decrease of plasma triglyceride levels (p = 0.0002) as well as with an increase of fasting glucose (FG) levels (p = 0.02). Age was associated with post-intervention plasma total cholesterol (p = 0.01), low-density lipoprotein cholesterol (p = 0.007), apolipoprotein B (p = 0.04), and insulin (p = 0.002) levels. Sex was associated with post-intervention plasma high-density lipoprotein cholesterol levels (p = 0.02). BMI was associated with plasma FG (p = 0.02) and insulin levels (p < 0.0001) after the supplementation. APOE genotype was associated with FG (p = 0.001) and C-reactive protein levels (p = 0.03) after the supplementation. CONCLUSION: Results suggest that age, sex, BMI, and the APOE genotype contribute to the inter-individual variability observed in the metabolic response to an n-3 PUFA supplementation.
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Apolipoproteínas E/genética , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Genótipo , Fatores Etários , Idoso , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Eicosapentaenoic and docosahexaenoic acids have been reported to have a variety of beneficial effects on cardiovascular disease risk factors. However, a large inter-individual variability in the plasma lipid response to an omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation is observed in different studies. Genetic variations may influence plasma lipid responsiveness. The aim of the present study was to examine the effects of a supplementation with n-3 PUFA on the plasma lipid profile in relation to the presence of single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster. A total of 208 subjects from Quebec City area were supplemented with 3 g/day of n-3 PUFA, during six weeks. In a statistical model including the effect of the genotype, the supplementation and the genotype by supplementation interaction, SNP rs174546 was significantly associated (p = 0.02) with plasma triglyceride (TG) levels, pre- and post-supplementation. The n-3 supplementation had an independent effect on plasma TG levels and no significant genotype by supplementation interaction effects were observed. In summary, our data support the notion that the FADS gene cluster is a major determinant of plasma TG levels. SNP rs174546 may be an important SNP associated with plasma TG levels and FADS1 gene expression independently of a nutritional intervention with n-3 PUFA.