FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease

• Published in: The American journal of clinical nutrition Vol. 88; no. 4; pp. 941 - 949
• Main Authors: Martinelli, Nicola, Girelli, Domenico, Malerba, Giovanni, Guarini, Patrizia, Illig, Thomas, Trabetti, Elisabetta, Sandri, Marco, Friso, Simonetta, Pizzolo, Francesca, Schaeffer, Linda, Heinrich, Joachim, Pignatti, Pier Franco, Corrocher, Roberto, Olivieri, Oliviero
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.10.2008; American Society for Clinical Nutrition; American Society for Clinical Nutrition, Inc
• Subjects: administration & dosage; arachidonic acid; Arachidonic Acid - administration & dosage; Arachidonic Acid - metabolism; atherosclerosis; Biological and medical sciences; C-reactive protein; Cardiovascular disease; chemistry; Coronary Artery Disease; Coronary Artery Disease - enzymology; Coronary Artery Disease - genetics; coronary vessels; Delta-5 Fatty Acid Desaturase; delta-6-desaturase; enzyme activity; Enzymes; enzymology; Erythrocyte Membrane; Erythrocyte Membrane - chemistry; Fatty Acid Desaturases; Fatty Acid Desaturases - genetics; Fatty Acid Desaturases - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic; genetics; genotype; Genotype & phenotype; Haplotypes; heart diseases; Humans; inflammation; Inflammation - enzymology; Inflammation - genetics; linoleic acid; Linoleic Acid - administration & dosage; Linoleic Acid - metabolism; Linoleoyl-CoA Desaturase; Linoleoyl-CoA Desaturase - genetics; Linoleoyl-CoA Desaturase - metabolism; lipid metabolism; Male; metabolism; Middle Aged; Multigene Family; nutrition-genotype interaction; Polymorphism; Polymorphism, Single Nucleotide; polyunsaturated fatty acids; Risk Factors; single nucleotide polymorphism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Cardiovascular disease; Genotype; Inflammation; Ratio; Arachidonic acid; Coronary heart disease; Linoleic acid
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.1093/ajcn/88.4.941

BACKGROUND: The δ-5 and δ-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 α-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). DESIGN: 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. CONCLUSION: 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.