Genetic Variation in FADS Has Little Effect on the Association between Dietary PUFA Intake and Cardiovascular Disease.
Hellstrand, Sophie LU ; Ericson, Ulrika LU ; Gullberg, Bo LU ; Hedblad, Bo LU ; Orho-Melander, Marju LU and Sonestedt, Emily LU
(2014)
In Journal of Nutrition
144(9).
p.1356-1363
- 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 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 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... (More)
- 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 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. Borderline interaction was observed between the α-linolenic acid (ALA) (18:3n-3)-to-linoleic acid (LA) (18:2n-6) intake ratio and FADS 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 FADS genotype on CVD incidence was strengthened and statistically significant (P = 0.04). Additionally, we observed a significant interaction between ALA and FADS 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 FADS 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4583199
- author
- Hellstrand, Sophie
LU
; Ericson, Ulrika
LU
; Gullberg, Bo
LU
; Hedblad, Bo
LU
; Orho-Melander, Marju
LU
and Sonestedt, Emily
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Nutrition
- volume
- 144
- issue
- 9
- pages
- 1356 - 1363
- publisher
- Oxford University Press
- external identifiers
-
- pmid:25008580
- wos:000340736300002
- scopus:84906903337
- pmid:25008580
- ISSN
- 1541-6100
- DOI
- 10.3945/jn.114.192708
- project
- Interaction between dietary factors and genetic risk for lipoprotein traits and cardiovascular disease
- language
- English
- LU publication?
- yes
- id
- 3aaf27df-cc8b-4596-a78a-c427f99eac56 (old id 4583199)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25008580?dopt=Abstract
- date added to LUP
- 2016-04-01 09:50:58
- date last changed
- 2022-01-25 17:18:39
@article{3aaf27df-cc8b-4596-a78a-c427f99eac56,
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 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 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. Borderline interaction was observed between the α-linolenic acid (ALA) (18:3n-3)-to-linoleic acid (LA) (18:2n-6) intake ratio and FADS 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 FADS genotype on CVD incidence was strengthened and statistically significant (P = 0.04). Additionally, we observed a significant interaction between ALA and FADS 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 FADS 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.}},
author = {{Hellstrand, Sophie and Ericson, Ulrika and Gullberg, Bo and Hedblad, Bo and Orho-Melander, Marju and Sonestedt, Emily}},
issn = {{1541-6100}},
language = {{eng}},
number = {{9}},
pages = {{1356--1363}},
publisher = {{Oxford University Press}},
series = {{Journal of Nutrition}},
title = {{Genetic Variation in FADS Has Little Effect on the Association between Dietary PUFA Intake and Cardiovascular Disease.}},
url = {{http://dx.doi.org/10.3945/jn.114.192708}},
doi = {{10.3945/jn.114.192708}},
volume = {{144}},
year = {{2014}},
}