TY - JOUR
T1 - Markers of endogenous desaturase activity and risk of coronary heart disease in the CAREMA cohort study
AU - Lu, Y.
AU - Vaarhorst, A.
AU - Merry, A.H.
AU - Dolle, M.E.T.
AU - Hovenier, R.
AU - Imholz, S.
AU - Schouten, L.J.
AU - Heijmans, B.T.
AU - Muller, M.R.
AU - Slagboom, P.E.
AU - van den Brandt, P.A.
AU - Gorgels, A.P.
AU - Boer, J.M.A.
AU - Feskens, E.J.M.
PY - 2012
Y1 - 2012
N2 - Background
Intakes of n-3 polyunsaturated fatty acids (PUFAs), especially EPA (C20:5n-3) and DHA (C22:6n-3), are known to prevent fatal coronary heart disease (CHD). The effects of n-6 PUFAs including arachidonic acid (C20:4n-6), however, remain unclear. d-5 and d-6 desaturases are rate-limiting enzymes for synthesizing long-chain n-3 and n-6 PUFAs. C20:4n-6 to C20:3n-6 and C18:3n-6 to C18:2n-6 ratios are markers of endogenous d-5 and d-6 desaturase activities, but have never been studied in relation to incident CHD. Therefore, the aim of this study was to investigate the relation between these ratios as well as genotypes of FADS1 rs174547 and CHD incidence.
Methods
We applied a case-cohort design within the CAREMA cohort, a large prospective study among the general Dutch population followed up for a median of 12.1 years. Fatty acid profile in plasma cholesteryl esters and FADS1 genotype at baseline were measured in a random subcohort (n = 1323) and incident CHD cases (n = 537). Main outcome measures were hazard ratios (HRs) of incident CHD adjusted for major CHD risk factors.
Results
The AA genotype of rs174547 was associated with increased plasma levels of C204n-6, C20:5n-3 and C22:6n-3 and increased d-5 and d-6 desaturase activities, but not with CHD risk. In multivariable adjusted models, high baseline d-5 desaturase activity was associated with reduced CHD risk (P for trend = 0.02), especially among those carrying the high desaturase activity genotype (AA): HR (95% CI) = 0.35 (0.15–0.81) for comparing the extreme quintiles. High plasma DHA levels were also associated with reduced CHD risk.
Conclusion
In this prospective cohort study, we observed a reduced CHD risk with an increased C20:4n-6 to C20:3n-6 ratio, suggesting that d-5 desaturase activity plays a role in CHD etiology. This should be investigated further in other independent studies
AB - Background
Intakes of n-3 polyunsaturated fatty acids (PUFAs), especially EPA (C20:5n-3) and DHA (C22:6n-3), are known to prevent fatal coronary heart disease (CHD). The effects of n-6 PUFAs including arachidonic acid (C20:4n-6), however, remain unclear. d-5 and d-6 desaturases are rate-limiting enzymes for synthesizing long-chain n-3 and n-6 PUFAs. C20:4n-6 to C20:3n-6 and C18:3n-6 to C18:2n-6 ratios are markers of endogenous d-5 and d-6 desaturase activities, but have never been studied in relation to incident CHD. Therefore, the aim of this study was to investigate the relation between these ratios as well as genotypes of FADS1 rs174547 and CHD incidence.
Methods
We applied a case-cohort design within the CAREMA cohort, a large prospective study among the general Dutch population followed up for a median of 12.1 years. Fatty acid profile in plasma cholesteryl esters and FADS1 genotype at baseline were measured in a random subcohort (n = 1323) and incident CHD cases (n = 537). Main outcome measures were hazard ratios (HRs) of incident CHD adjusted for major CHD risk factors.
Results
The AA genotype of rs174547 was associated with increased plasma levels of C204n-6, C20:5n-3 and C22:6n-3 and increased d-5 and d-6 desaturase activities, but not with CHD risk. In multivariable adjusted models, high baseline d-5 desaturase activity was associated with reduced CHD risk (P for trend = 0.02), especially among those carrying the high desaturase activity genotype (AA): HR (95% CI) = 0.35 (0.15–0.81) for comparing the extreme quintiles. High plasma DHA levels were also associated with reduced CHD risk.
Conclusion
In this prospective cohort study, we observed a reduced CHD risk with an increased C20:4n-6 to C20:3n-6 ratio, suggesting that d-5 desaturase activity plays a role in CHD etiology. This should be investigated further in other independent studies
KW - dietary arachidonic-acid
KW - n-6 fatty-acids
KW - genome-wide association
KW - cardiovascular-disease
KW - delta-6 desaturase
KW - genetic-variation
KW - loci
KW - expression
KW - humans
KW - metabolism
U2 - 10.1371/journal.pone.0041681
DO - 10.1371/journal.pone.0041681
M3 - Article
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e41681
ER -
