Genetic profiling of fatty acid desaturase polymorphisms identifies patients who may benefit from high-dose omega-3 fatty acids in cardiac remodeling after acute myocardial infarction—Post-hoc analysis from the OMEGA-REMODEL randomized controlled trial

Autoři: Raymond Y. Kwong aff001;  Bobak Heydari aff003;  Yin Ge aff001;  Shuaib Abdullah aff001;  Kana Fujikura aff001;  Kyoichi Kaneko aff001;  William S. Harris aff004;  Michael Jerosch-Herold aff001;  Elliott M. Antman aff002;  Jonathan G. Seidman aff006;  Marc A. Pfeffer aff002
Působiště autorů: Noninvasive Cardiovascular Imaging Section, Cardiovascular Division, Department of Medicine and Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America aff001;  Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America aff002;  Cardiovascular Division, Department of Medicine, University of Calgary, Calgary, Alberta, Canada aff003;  Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Fall, South Dakota, United States of America aff004;  OmegaQuant Analytics, LLC, Sioux Falls, South Dakota, United States of America aff005;  Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222061



The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes.

Methods and results

We tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, p<0.0001; vs. AG: 1.76±0.35, p = 0.03). When randomized to 6-months of O-3FA treatment, GG patients demonstrated significant lowering of LV end-systolic volume index (LVESVi), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and galectin-3 levels compared to placebo (-4.4 vs. 1.2 ml/m2, -733 vs. -181 pg/mL, and -2.0 vs. 0.5 ng/mL; p = 0.006, 0.006, and 0.03, respectively). In contrast, patients with either AA or AG genotype did not demonstrate significant lowering of LVESVi, NT-proBNP, or galectin-3 levels from O-3FA treatment, compared to placebo. The odds ratios for improving LVESVi by 10% with O-3FA treatment was 7.2, 1.6, and 1.2 in patients with GG, AG, and AA genotypes, respectively.


Genetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI.

Clinical trial registration information Identifier: NCT00729430.

Klíčová slova:

Biology and life sciences – Biochemistry – Lipids – Fatty acids – Biomarkers – Proteins – Lipoproteins – Developmental biology – Fibrosis – Genetics – Heredity – Genetic mapping – Variant genotypes – Medicine and health sciences – Immunology – Immune response – Inflammation – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine – Cardiology – Myocardial infarction – Vascular medicine – Coronary heart disease


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