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 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. A borderline interaction was observed between the α-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.

FIGURE 1

Association between the ALA-to-LA intake ratio and incidence of CVD according to FADS1 rs174546 genotype CC (A), CT (B), and TT (C) among 24,032 participants in the Malmö Diet and Cancer cohort. Cox proportional hazard regression was used to calculate HR for each quintile of PUFA intake, with the lowest quintile as reference. Multivariate models were adjusted for age, sex, BMI, diet assessment method version, season, total energy intake, alcohol intake, leisure time physical activity, education, and smoking. The median ALA-to-LA intake ratio and n per quintile: quintile 1 = 0.12, n = 4806; quintile 2 = 0.14, n = 4807; quintile 3 = 0.15, n = 4806; quintile 4 = 0.17, n = 4807; and quintile 5 = 0.21, n = 4806. ALA, α-linolenic acid; CVD, cardiovascular disease; FADS1, fatty acid desaturase 1; LA, linoleic acid; Q, quintile.