Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study

Miles, Elizabeth; Kofler, Barbara; Curtis, Peter J.; Armah, Christopher K.; Kimber, Alan; Grew, J P; Farrell, Lesley; Stannard, Julie; Napper, Frances L.; Sala‐Vila, Aleix; West, Annette L.; Mathers, John C.; Packard, Christopher J.; Williams, Christine M.; Calder, Philip C.; Minihane, Anne Marie

doi:10.1093/ajcn/88.3.618

Cited by 148 publications

(166 citation statements)

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“…Intakes in the range of 0.7-1.5 g/day provided either as oily fish (Griffin et al 2006) or as purified lipids (Caslake et al 2008) in healthy subjects have shown a small effect on lowering TAG (8-11 %) and a 2-3 % increase in LDL-cholesterol concentration. With regard to the plasma lipid profile, we previously found a 15 % reduction in TAG concentration in women after 1.8 g/day, showing a clear dose-response relationship with increasing intakes (P = 0.002), but no significant effect on lipoprotein-cholesterol (Sanders et al 2011).…”

Section: Discussionmentioning

confidence: 99%

ELOVL2 gene polymorphisms are associated with increases in plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement

et al. 2013

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Fish oil supplementation provides an inconsistent degree of protection from cardiovascular disease (CVD), which may be attributed to genetic variation. Single nucleotide polymorphisms (SNPs) in the elongation-ofvery-long-chain-fatty-acids-2 (ELOVL2) gene have been strongly associated with plasma proportions of n-3 longchain polyunsaturated fatty acids (LC-PUFA). We investigated the effect of genotype interaction with fish oil dosage on plasma n-3 LC-PUFA proportions in a parallel doubleblind controlled trial, involving 367 subjects randomised to treatment with 0.45, 0.9 and 1.8 g/day eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1.51:1) or olive oil placebo for 6 months. We genotyped 310 subjects for ELOVL2 gene SNPs rs3734398, rs2236212 and rs953413. At baseline, carriers of all minor alleles had lower proportions of plasma DHA than non-carriers (P = 0.021-0.030). Interaction between genotype and treatment was a significant determinant of plasma EPA (P \ 0.0001) and DHA (P = 0.004-0.032). After the 1.8 g/day dose, carriers of ELOVL2 SNP minor alleles had approximately 30 % higher proportions of EPA (P = 0.002-0.004) and 9 % higher DHA (P = 0.013-0.017) than non-carriers. Minor allele carriers could therefore particularly benefit from a high intake of EPA and DHA in maintaining high levels of plasma n-3 PUFA conducive to protection from CVD.

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Section: Discussionmentioning

confidence: 99%

ELOVL2 gene polymorphisms are associated with increases in plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement

et al. 2013

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“…Fatty acid methyl esters were identified by comparison of retention times against known standards, Supelco 37 component FAME mix and PUFA-3 Menhaden oil (Supelco). Due to previous findings that changes in lipid profile in response to DHA supplementation differ between apoE4 carriers v. non-carriers (6,12,13) , phospholipid fatty acid status was analysed with respect to genotype in order to ascertain whether the E4 isoform may alter incorporation of LC n-3 PUFA into phospholipids. To our knowledge, only two studies have examined phospholipid fatty acid status with respect to genotype (6,14) , both with relatively small subject numbers (n 8 carriers, n 20 non-carriers and n 18 carriers, n 20 non-carriers, respectively).…”

Section: Assessment Of Plasma Phospholipid Fatty Acid Statusmentioning

confidence: 99%

SATgenɛ dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods

et al. 2012

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Response to dietary fat manipulation is highly heterogeneous, yet generic population-based recommendations aimed at reducing the burden of CVD are given. The APOE epsilon genotype has been proposed to be an important determinant of this response. The present study reports on the dietary strategy employed in the SATgen1 (SATurated fat and gene APOE) study, to assess the impact of altered fat content and composition on the blood lipid profile according to the APOE genotype. A flexible dietary exchange model was developed to implement three isoenergetic diets: a low-fat (LF) diet (target composition: 24 % of energy (%E) as fat, 8 %E SFA and 59 %E carbohydrate), a high-saturated fat (HSF) diet (38 %E fat, 18 %E SFA and 45 %E carbohydrate) and a HSF-DHA diet (HSF diet with 3 g DHA/d). Free-living participants (n 88; n 44 E3/E3 and n 44 E3/E4) followed the diets in a sequential design for 8 weeks, each using commercially available spreads, oils and snacks with specific fatty acid profiles. Dietary compositional targets were broadly met with significantly higher total fat (42·8 %E and 41·0 %E v. 25·1 %E, P#0·0011) and SFA (19·3 %E and 18·6 %E v. 8·33 %E, P# 0·0011) intakes during the HSF and HSF-DHA diets compared with the LF diet, in addition to significantly higher DHA intake during the HSF-DHA diet (P#0·0011). Plasma phospholipid fatty acid analysis revealed a 2-fold increase in the proportion of DHA after consumption of the HSF-DHA diet for 8 weeks, which was independent of the APOE genotype. In summary, the dietary strategy was successfully implemented in a free-living population resulting in well-tolerated diets which broadly met the dietary targets set.Key words: Dietary fat composition: APOE genotype: SFA: DHA In order to reduce the risk of CVD, the UK Scientific Advisory Committee on Nutrition (SACN) recommends a population reduction of dietary saturated fat (SFA) intake to an average of ,11 % of food energy and a minimum daily intake of 0·45 g of the long-chain n-3 PUFA (LC n-3 PUFA), EPA and DHA (1) . There is a rapidly increasing body of evidence on the significant impact of genetic variation and other physiological and lifestyle factors on an individual's response to dietary manipulation, and a recognition of the large interindividual heterogeneity in response to dietary change. In light of this, it is predicted that a more personalised/stratified approach to nutritional advice may be more effective in the reduction of disease risk (2) relative to the more generic advice currently provided. Available evidence examining genotype -diet -phenotype associations is largely derived from epidemiological studies, with data from 'fit-for-purpose' randomised controlled trials distinctly lacking.ApoE is a structural component of TAG-rich lipoproteins required for lipid transport and clearance. There are a number of SNP of the gene encoding for this apolipoprotein. The most studied are the APOE epsilon missense mutations rs429358 and rs7412 that give rise to three common isoforms (Apo12, Apo13 and Apo14). Thes...

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“…However, a number of studies are expected to report in the near future, including a prospective study of the impact of apo E genotype on blood lipid responses to fish oil fatty acids, which has also been designed to include equal numbers of both genders in each genotypic sub-group [44]. Evidence of gender-specific differences in response to diet that may be mediated in part by gender-genotype interactions is another factor that has recently been described in a few publications [4,40,45]. Evidence from studies involving functional proteins involved in lipid metabolism as related to cardiovascular disease (apo E), obesity (perilipin) and selenium metabolism (Selenoprotein P) is indicating that the differences in response to dietary modifications associated with specific genetic mutations may affect men and women differently.…”

Section: Genetic Variation and Nutritionmentioning

confidence: 99%

The challenges for molecular nutrition research 1: linking genotype to healthy nutrition

Williams¹,

Ordovas

Lairon

et al. 2008

Genes Nutr

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Nutrition science finds itself at a major crossroad. On the one hand we can continue the current path, which has resulted in some substantial advances, but also many conflicting messages which impair the trust of the general population, especially those who are motivated to improve their health through diet. The other road is uncharted and is being built over the many exciting new developments in life sciences. This new era of nutrition recognizes the complex relation between the health of the individual, its genome, and the life-long dietary exposure, and has lead to the realisation that nutrition is essentially a gene-environment interaction science. This review on the relation between genotype, diet and health is the first of a series dealing with the major challenges in molecular nutrition, analyzing the foundations of nutrition research. With the unravelling of the human genome and the linking of its variability to a multitude of phenotypes from ''healthy'' to an enormously complex range of predispositions, the dietary modulation of these propensities has become an area of active research. Classical genetic approaches applied so far in medical genetics have steered away from incorporating dietary effects in their models and paradoxically, most genetic studies analyzing diet-associated phenotypes and diseases simply ignore diet. Yet, a modest but increasing number of studies are accounting for diet as a modulator of genetic associations. These range from observational cohorts to intervention studies with prospectively selected genotypes. New statistical and All authors are member of The European Nutrigenomics Organisation (http://www.nugo.org). bioinformatics approaches are becoming available to aid in design and evaluation of these studies. This review discusses the various approaches used and provides concrete recommendations for future research. C. M. Williams (&)Hugh

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Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study

Cited by 148 publications

References 49 publications

ELOVL2 gene polymorphisms are associated with increases in plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement

ELOVL2 gene polymorphisms are associated with increases in plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement

SATgenɛ dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods

The challenges for molecular nutrition research 1: linking genotype to healthy nutrition

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