FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease.
BACKGROUND
The delta-5 and delta-6 desaturases, encoded by FADS1 and FADS2 genes, are key enzymes in polyunsaturated fatty acid (PUFA) metabolism that catalyze the conversion of linoleic acid (LA) into arachidonic acid (AA) and that of alpha-linolenic acid (ALA) into eicosapentaenoic acid (EPA). Single-nucleotide polymorphisms (SNPs) in FADS1 and FADS2 have been associated with different concentrations of AA and LA, and those associations have possible functional consequences for desaturase activity.


OBJECTIVE
We aimed to evaluate the possible association among FADS genotypes, desaturase activity, inflammation, and coronary artery disease (CAD).


METHODS
Thirteen FADS SNPs and the ratio of AA to LA (AA/LA) on red blood cell (RBC) membranes, a marker of desaturase activity, were evaluated in 876 subjects with (n = 610) or without (n = 266) angiographically documented CAD.


RESULTS
Both AA/LA and the ratio of EPA to ALA (EPA/ALA) were higher in patients with CAD than in those without CAD, but, in a multiple logistic regression model, only a higher AA/LA resulted an independent risk factor for CAD (odds ratio: 2.55; 95% CI: 1.61, 4.05 for higher compared with lower ratio tertile; P for trend < 0.001). Furthermore, concentrations of high-sensitivity C-reactive protein increased progressively across tertiles of AA/LA. Graded increases in high-sensitivity C-reactive protein concentrations and CAD risk were related to the carriership of FADS haplotypes, including the alleles associated with a higher ratio.


CONCLUSIONS
In populations following a Western diet, subjects carrying FADS haplotypes that are associated with higher desaturase activity may be prone to a proinflammatory response favoring atherosclerotic vascular damage.
Department of Clinical and Experimental Medicine and the Section of Biology and Genetics, University of Verona, Verona, Italy.
Nicola
N
Martinelli
Domenico
D
Girelli
Giovanni
G
Malerba
Patrizia
P
Guarini
Thomas
T
Illig
Elisabetta
E
Trabetti
Marco
M
Sandri
Simonetta
S
Friso
Francesca
F
Pizzolo
Linda
L
Schaeffer
Joachim
J
Heinrich
Pier Franco
PF
Pignatti
Roberto
R
Corrocher
Oliviero
O
Olivieri
D016718:Arachidonic Acid / Q000008:administration & dosage* / Q000378:metabolism; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D000090943:Delta-5 Fatty Acid Desaturase; D004910:Erythrocyte Membrane / Q000737:chemistry; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics*; D019787:Linoleic Acid / Q000008:administration & dosage* / Q000378:metabolism; D050602:Linoleoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D000090943:Delta-5 Fatty Acid Desaturase; D016718:Arachidonic Acid; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; D050602:Linoleoyl-CoA Desaturase