Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: a secondary analysis of the seAFOod polyp prevention trial.

Autor:	Sun G; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Li YN; Department of Pediatrics, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, TX, United States; Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, United States., Davies JR; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Block RC; Department of Public Health Sciences, University of Rochester, Rochester, NY, United States; Cardiovascular Division of the Department of Medicine, University of Rochester, Rochester, NY, United States; Center for Community Health and Prevention, University of Rochester, Rochester, NY, United States., Kothapalli KS; Department of Pediatrics, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, TX, United States; Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, United States., Brenna JT; Department of Pediatrics, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, TX, United States; Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, United States., Hull MA; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom. Electronic address: m.a.hull@leeds.ac.uk.
Jazyk:	angličtina
Zdroj:	The American journal of clinical nutrition [Am J Clin Nutr] 2024 Aug; Vol. 120 (2), pp. 360-368. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1016/j.ajcnut.2024.06.004
Abstrakt:	Background: A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences the expression of FADS1, which controls the synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for proinflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs. Objectives: We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2×2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 mo (ISRCTN05926847). Methods: Participant Indel genotype was determined by polymerase chain reaction (PCR) blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention with its placebo. Presence of ≥1 Indel I allele and an interaction term (I allele × active intervention) were covariates. Results: In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR]: 0.92; 95% confidence interval: 0.74, 1.16), mirroring original seAFOod trial analysis. However, the presence of ≥1 I allele identified EPA users with a significant reduction in colorectal polyp number (IRR: 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR. Conclusions: The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted. The seAFOod polyp prevention trial and STOP-ADENOMA study were registered at International Standard Randomised Controlled Trial Number registry as ISRCTN05926847. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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