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Genetic variation in FADS1 has little effect on the association between dietary PUFA intake and cardiovascular disease.

ABSTRACT: The unclear link between intake of polyunsaturated fatty acids (PUFAs) and risk of cardiovascular disease (CVD) could depend on genetic differences between individuals. Minor alleles of single-nucleotide polymorphisms (SNPs) in the ?5 fatty acid desaturase (FADS) 1 gene were associated with lower blood concentrations of long-chain ?-3 (n-3) and ?-6 (n-6) PUFAs, indicating an associated loss of function effect. We examined whether the SNP rs174546 in FADS1 modifies the association between PUFA intakes and CVD risk. We included 24,032 participants (62% women, aged 44-74 y) from the Malmö Diet and Cancer cohort without prevalent CVD and diabetes. During a mean follow-up of 14 y, 2648 CVD cases were identified. Diet was assessed by a modified diet history method. A borderline interaction was observed between the ?-linolenic acid (ALA) (18:3n-3)-to-linoleic acid (LA) (18:2n-6) intake ratio and FADS1 genotype on CVD incidence (P = 0.06). The ALA-to-LA intake ratio was inversely associated with CVD risk only among participants homozygous for the minor T-allele (HR for quintile 5 vs. quintile 1 = 0.72; 95% CI: 0.50, 1.04; P-trend = 0.049). When excluding participants reporting unstable food habits in the past (35%), the interaction between the ALA-to-LA intake ratio and FADS1 genotype on CVD incidence was strengthened and statistically significant (P = 0.04). Additionally, we observed a significant interaction between ALA and FADS1 genotype on ischemic stroke incidence (P = 0.03). ALA was inversely associated with ischemic stroke only among TT genotype carriers (HR for quintile 5 vs. quintile 1 = 0.50; 95% CI: 0.27, 0.94; P-trend = 0.02). In this large cohort, we found some weak, but not convincing, evidence of effect modification by genetic variation in FADS1 on the associations between PUFA intakes and CVD risk. For the 11% of the population homozygous for the minor T-allele of rs174546 that associates with lower ?5 FADS activity, high ALA intake and ALA-to-LA intake ratio may be preferable in the prevention of CVD and ischemic stroke.

SUBMITTER: Hellstrand S

PROVIDER: S-EPMC4130826 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Genetic variation in FADS1 has little effect on the association between dietary PUFA intake and cardiovascular disease.

Hellstrand Sophie S Ericson Ulrika U Gullberg Bo B Hedblad Bo B Orho-Melander Marju M Sonestedt Emily E

The Journal of nutrition 20140709 9

The unclear link between intake of polyunsaturated fatty acids (PUFAs) and risk of cardiovascular disease (CVD) could depend on genetic differences between individuals. Minor alleles of single-nucleotide polymorphisms (SNPs) in the ∆5 fatty acid desaturase (FADS) 1 gene were associated with lower blood concentrations of long-chain ω-3 (n-3) and ω-6 (n-6) PUFAs, indicating an associated loss of function effect. We examined whether the SNP rs174546 in FADS1 modifies the association between PUFA in ...[more]

PMID: 25008580

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Project description:BACKGROUND: Elevated cholesterol levels in children can be a risk factor for cardiovascular diseases in later life. In adults, it has been shown that blood lipid levels are strongly influenced by polymorphisms in the fatty acid desaturase (FADS) gene cluster in addition to nutritional and other exogenous and endogenous determinants. Our aim was to investigate whether lipid levels are determined by the FADS genotype already in children and whether this association interacts with dietary intake of n-3 fatty acids. METHODS: The analysis was based on data of 2006 children from two German prospective birth cohort studies. Total cholesterol, HDL, LDL and triglycerides were measured at 10 years of age. Six single nucleotide polymorphisms (SNPs) of the FADS gene cluster were genotyped. Dietary n-3 fatty acid intake was assessed by food frequency questionnaire. Linear regression modeling was used to assess the association between lipid levels, n-3 fatty acid intake and FADS genotype. RESULTS: Individuals carrying the homozygous minor allele had lower levels of total cholesterol [means ratio (MR) ranging from 0.96 (p?=?0.0093) to 0.98 (p?=?0.2949), depending on SNPs] and LDL [MR between 0.94 (p?=?0.0179) and 0.97 (p?=?0.2963)] compared to homozygous major allele carriers. Carriers of the heterozygous allele showed lower HDL levels [? between -0.04 (p?=?0.0074) to -0.01 (p?=?0.3318)] and higher triglyceride levels [MR ranging from 1.06 (p?=?0.0065) to 1.07 (p?=?0.0028)] compared to homozygous major allele carriers. A higher n-3 PUFA intake was associated with higher concentrations of total cholesterol, LDL, HDL and lower triglyceride levels, but these associations did not interact with the FADS1 FADS2 genotype. CONCLUSION: Total cholesterol, HDL, LDL and triglyceride concentrations may be influenced by the FADS1 FADS2 genotype already in 10 year old children. Genetically determined blood lipid levels during childhood might differentially predispose individuals to the development of cardiovascular diseases later in life.

Project description:BACKGROUND:Circadian rhythms across mammalian tissues are coordinated by a master clock in the suprachiasmatic nucleus (SCN) that is principally entrained by light-dark cycles. Prior investigations have shown, however, that time-restricted feeding (TRF)-daily alternation of fasting and food availability-synchronizes peripheral clocks independent of the light-dark cycle and of the SCN. This has led to the idea that downstream peripheral clocks are entrained indirectly by food intake rhythms. However, TRF is not a normal eating pattern, and it imposes non-physiologic long fasts that rodents do not typically experience. Therefore, we tested whether normal feeding patterns can phase-shift or entrain peripheral tissues by measuring circadian rhythms of the liver, kidney, and submandibular gland in mPer2Luc mice under different food schedules. RESULTS:We employed home cage feeders to first measure ad libitum food intake and then to dispense 20-mg pellets on a schedule mimicking that pattern. In both conditions, PER2::LUC bioluminescence peaked during the night as expected. Surprisingly, shifting the scheduled feeding by 12?h advanced peripheral clocks by only 0-3?h, much less than predicted from TRF protocols. To isolate the effects of feeding from the light-dark cycle, clock phase was then measured in mice acclimated to scheduled feeding over the course of 3 months in constant darkness. In these conditions, peripheral clock phases were better predicted by the rest-activity cycle than by the food schedule, contrary to expectation based on TRF studies. At the end of both experiments, mice were exposed to a modified TRF with food provided in eight equally sized meals over 12?h. In the light-dark cycle, this advanced the phase of the liver and kidney, though less so than in TRF with ad libitum access; in darkness, this entrained the liver and kidney but had little effect on the submandibular gland or the rest-activity cycle. CONCLUSIONS:These data suggest that natural feeding patterns can only weakly affect circadian clocks. Instead, in normally feeding mice, the central pacemaker in the brain may set the phase of peripheral organs via pathways that are independent of feeding behavior.

Dataset Information

Genetic variation in FADS1 has little effect on the association between dietary PUFA intake and cardiovascular disease.

Publications

Genetic variation in FADS1 has little effect on the association between dietary PUFA intake and cardiovascular disease.

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