Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 426865
Title Markers of endogenous desaturase activity and risk of coronary heart disease in the CAREMA cohort study
Author(s) Lu, Y.; Vaarhorst, A.; Merry, A.H.; Dolle, M.E.T.; Hovenier, R.; Imholz, S.; Schouten, L.J.; Heijmans, B.T.; Muller, M.R.; Slagboom, P.E.; Brandt, P.A. van den; Gorgels, A.P.; Boer, J.M.A.; Feskens, E.J.M.
Source PLoS One 7 (2012)7. - ISSN 1932-6203
Department(s) Chair Nutrition Metabolism and Genomics
Chair Nutrition and Disease
Publication type Refereed Article in a scientific journal
Publication year 2012
Keyword(s) dietary arachidonic-acid - n-6 fatty-acids - genome-wide association - cardiovascular-disease - delta-6 desaturase - genetic-variation - loci - expression - humans - metabolism
Abstract 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
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