Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study.
BACKGROUND
The delta-5 and delta-6 desaturases, encoded by the FADS1 and FADS2 genes, are rate-limiting enzymes in polyunsaturated fatty acid (PUFA) biosynthesis. Single nucleotide polymorphisms in the FADS gene cluster region have been associated with both PUFA concentrations in plasma or erythrocyte membrane phospholipids and cholesterol concentrations in recent genome-wide association studies.


OBJECTIVE
We examined whether genetic variations in the FADS gene cluster region interact with dietary intakes of n-3 (omega-3) and n-6 (omega-6) PUFAs to affect plasma total, HDL-, and non-HDL-cholesterol concentrations.


METHODS
Dietary intakes of n-3 and n-6 PUFAs, plasma concentrations of total and HDL cholesterol, and rs174546, rs482548, and rs174570 in the FADS gene cluster region were measured in 3575 subjects in the second survey of the Doetinchem Cohort Study.


RESULTS
Significant associations between rs174546 genotypes and total and non-HDL-cholesterol concentrations were observed in the group with a high intake of n-3 PUFAs (> or =0.51% of total energy; P = 0.006 and 0.047, respectively) but not in the low-intake group (P for interaction = 0.32 and 0.51, respectively). The C allele was associated with high total and non-HDL-cholesterol concentrations. Furthermore, the C allele was significantly associated with high HDL-cholesterol concentrations in the group with a high intake of n-6 PUFAs (> or =5.26% of total energy, P = 0.004) but not in the group with a low intake (P for interaction = 0.02).


CONCLUSIONS
Genetic variation in the FADS1 gene potentially interacts with dietary PUFA intakes to affect plasma cholesterol concentrations, which should be investigated further in other studies.
Lu
Yingchang
Y
Division of Human Nutrition, Wageningen University Research Center, Wageningen, Netherlands. kevin.lu@wur.nl
Feskens
Edith Jm
EJ
Dollé
Martijn Et
ME
Imholz
Sandra
S
Verschuren
Wm Monique
WM
Müller
Michael
M
Boer
Jolanda Ma
JM
D020413:3' Untranslated Regions / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide
D020413:3' Untranslated Regions; D001055:Apolipoproteins B; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D000090943:Delta-5 Fatty Acid Desaturase; D002784:Cholesterol; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human