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FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease.
Am J Clin Nutr. 2008 Oct; 88(4):941-9.AJ

Abstract

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).

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.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and the Section of Biology and Genetics, University of Verona, Verona, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18842780

Citation

Martinelli, Nicola, et al. "FADS Genotypes and Desaturase Activity Estimated By the Ratio of Arachidonic Acid to Linoleic Acid Are Associated With Inflammation and Coronary Artery Disease." The American Journal of Clinical Nutrition, vol. 88, no. 4, 2008, pp. 941-9.
Martinelli N, Girelli D, Malerba G, et al. FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. Am J Clin Nutr. 2008;88(4):941-9.
Martinelli, N., Girelli, D., Malerba, G., Guarini, P., Illig, T., Trabetti, E., Sandri, M., Friso, S., Pizzolo, F., Schaeffer, L., Heinrich, J., Pignatti, P. F., Corrocher, R., & Olivieri, O. (2008). FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. The American Journal of Clinical Nutrition, 88(4), 941-9.
Martinelli N, et al. FADS Genotypes and Desaturase Activity Estimated By the Ratio of Arachidonic Acid to Linoleic Acid Are Associated With Inflammation and Coronary Artery Disease. Am J Clin Nutr. 2008;88(4):941-9. PubMed PMID: 18842780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. AU - Martinelli,Nicola, AU - Girelli,Domenico, AU - Malerba,Giovanni, AU - Guarini,Patrizia, AU - Illig,Thomas, AU - Trabetti,Elisabetta, AU - Sandri,Marco, AU - Friso,Simonetta, AU - Pizzolo,Francesca, AU - Schaeffer,Linda, AU - Heinrich,Joachim, AU - Pignatti,Pier Franco, AU - Corrocher,Roberto, AU - Olivieri,Oliviero, PY - 2008/10/10/pubmed PY - 2008/11/5/medline PY - 2008/10/10/entrez SP - 941 EP - 9 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 88 IS - 4 N2 - 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). 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/18842780/FADS_genotypes_and_desaturase_activity_estimated_by_the_ratio_of_arachidonic_acid_to_linoleic_acid_are_associated_with_inflammation_and_coronary_artery_disease_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.1093/ajcn/88.4.941 DB - PRIME DP - Unbound Medicine ER -