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

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...

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Published in:PloS one 2019-09, Vol.14 (9), p.e0222061
Main Authors: Kwong, Raymond Y, Heydari, Bobak, Ge, Yin, Abdullah, Shuaib, Fujikura, Kana, Kaneko, Kyoichi, Harris, William S, Jerosch-Herold, Michael, Antman, Elliott M, Seidman, Jonathan G, Pfeffer, Marc A
Format: Article
Language:English
Subjects:
Adenine
Aged
Analysis
Arachidonic acid
Arachidonic Acid - blood
Attenuation
Biology and Life Sciences
Brain natriuretic peptide
Cardiovascular disease
Care and treatment
Clinical trials
Criminal investigation
Desaturase
Double-Blind Method
Drug dosages
Enzymes
Fatty Acid Desaturases - genetics
Fatty acids
Fatty Acids, Omega-3 - administration & dosage
Fatty Acids, Omega-3 - pharmacology
Female
Fibrosis
Galectin-3
Gene polymorphism
Genes
Genetic aspects
Genetic polymorphisms
Genomes
Genotypes
Guanine
Heart
Heart attack
Heart attacks
Hospitals
Humans
Inflammation
Linoleic acid
Linoleic Acid - blood
Lipids
Male
Medicine
Medicine and Health Sciences
Middle Aged
Myocardial infarction
Myocardial Infarction - blood
Myocardial Infarction - drug therapy
Myocardial Infarction - genetics
Natriuretic peptides
Omega 3 fatty acids
Patients
Peptides
Pharmacogenomic Variants
Polymorphism
Polymorphism, Single Nucleotide
Polyunsaturated fatty acids
Prospective Studies
Pulmonary arteries
Purines
Retirement benefits
Tertiary Care Centers
Treatment Outcome
Ventricular Remodeling - drug effects
Womens health
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cited_by cdi_FETCH-LOGICAL-c692t-f851440794688193593a1f347094e5514ec0f1cf01b13f741cec68f7a5f708733
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container_issue 9
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container_title PloS one
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creator Kwong, Raymond Y
Heydari, Bobak
Ge, Yin
Abdullah, Shuaib
Fujikura, Kana
Kaneko, Kyoichi
Harris, William S
Jerosch-Herold, Michael
Antman, Elliott M
Seidman, Jonathan G
Pfeffer, Marc A
description 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. 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
doi_str_mv 10.1371/journal.pone.0222061
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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. 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&lt;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. clinicaltrials.gov Identifier: NCT00729430.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0222061</identifier><identifier>PMID: 31532795</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenine ; Aged ; Analysis ; Arachidonic acid ; Arachidonic Acid - blood ; Attenuation ; Biology and Life Sciences ; Brain natriuretic peptide ; Cardiovascular disease ; Care and treatment ; Clinical trials ; Criminal investigation ; Desaturase ; Double-Blind Method ; Drug dosages ; Enzymes ; Fatty Acid Desaturases - genetics ; Fatty acids ; Fatty Acids, Omega-3 - administration &amp; dosage ; Fatty Acids, Omega-3 - pharmacology ; Female ; Fibrosis ; Galectin-3 ; Gene polymorphism ; Genes ; Genetic aspects ; Genetic polymorphisms ; Genomes ; Genotypes ; Guanine ; Heart ; Heart attack ; Heart attacks ; Hospitals ; Humans ; Inflammation ; Linoleic acid ; Linoleic Acid - blood ; Lipids ; Male ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Myocardial infarction ; Myocardial Infarction - blood ; Myocardial Infarction - drug therapy ; Myocardial Infarction - genetics ; Natriuretic peptides ; Omega 3 fatty acids ; Patients ; Peptides ; Pharmacogenomic Variants ; Polymorphism ; Polymorphism, Single Nucleotide ; Polyunsaturated fatty acids ; Prospective Studies ; Pulmonary arteries ; Purines ; Retirement benefits ; Tertiary Care Centers ; Treatment Outcome ; Ventricular Remodeling - drug effects ; Womens health</subject><ispartof>PloS one, 2019-09, Vol.14 (9), p.e0222061</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Kwong et al. 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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. 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&lt;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. clinicaltrials.gov Identifier: NCT00729430.</description><subject>Adenine</subject><subject>Aged</subject><subject>Analysis</subject><subject>Arachidonic acid</subject><subject>Arachidonic Acid - blood</subject><subject>Attenuation</subject><subject>Biology and Life Sciences</subject><subject>Brain natriuretic peptide</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Criminal investigation</subject><subject>Desaturase</subject><subject>Double-Blind Method</subject><subject>Drug dosages</subject><subject>Enzymes</subject><subject>Fatty Acid Desaturases - genetics</subject><subject>Fatty acids</subject><subject>Fatty Acids, Omega-3 - administration &amp; dosage</subject><subject>Fatty Acids, Omega-3 - pharmacology</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Galectin-3</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genomes</subject><subject>Genotypes</subject><subject>Guanine</subject><subject>Heart</subject><subject>Heart attack</subject><subject>Heart attacks</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Linoleic acid</subject><subject>Linoleic Acid - blood</subject><subject>Lipids</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - blood</subject><subject>Myocardial Infarction - drug therapy</subject><subject>Myocardial Infarction - genetics</subject><subject>Natriuretic peptides</subject><subject>Omega 3 fatty acids</subject><subject>Patients</subject><subject>Peptides</subject><subject>Pharmacogenomic Variants</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Polyunsaturated fatty acids</subject><subject>Prospective Studies</subject><subject>Pulmonary arteries</subject><subject>Purines</subject><subject>Retirement benefits</subject><subject>Tertiary Care Centers</subject><subject>Treatment Outcome</subject><subject>Ventricular Remodeling - drug effects</subject><subject>Womens 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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</title><author>Kwong, Raymond Y ; Heydari, Bobak ; Ge, Yin ; Abdullah, Shuaib ; Fujikura, Kana ; Kaneko, Kyoichi ; Harris, William S ; Jerosch-Herold, Michael ; Antman, Elliott M ; Seidman, Jonathan G ; Pfeffer, Marc A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-f851440794688193593a1f347094e5514ec0f1cf01b13f741cec68f7a5f708733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenine</topic><topic>Aged</topic><topic>Analysis</topic><topic>Arachidonic acid</topic><topic>Arachidonic Acid - blood</topic><topic>Attenuation</topic><topic>Biology and Life Sciences</topic><topic>Brain natriuretic 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Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwong, Raymond Y</au><au>Heydari, Bobak</au><au>Ge, Yin</au><au>Abdullah, Shuaib</au><au>Fujikura, Kana</au><au>Kaneko, Kyoichi</au><au>Harris, William S</au><au>Jerosch-Herold, Michael</au><au>Antman, Elliott M</au><au>Seidman, Jonathan G</au><au>Pfeffer, Marc A</au><au>Andò, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-09-18</date><risdate>2019</risdate><volume>14</volume><issue>9</issue><spage>e0222061</spage><pages>e0222061-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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. 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&lt;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. clinicaltrials.gov Identifier: NCT00729430.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31532795</pmid><doi>10.1371/journal.pone.0222061</doi><tpages>e0222061</tpages><orcidid>https://orcid.org/0000-0001-8212-0759</orcidid><orcidid>https://orcid.org/0000-0001-9018-6731</orcidid><orcidid>https://orcid.org/0000-0002-0808-9199</orcidid><orcidid>https://orcid.org/0000-0001-7610-850X</orcidid><orcidid>https://orcid.org/0000-0002-5231-0866</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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1932-6203
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source Publicly Available Content Database; PubMed Central
subjects Adenine
Aged
Analysis
Arachidonic acid
Arachidonic Acid - blood
Attenuation
Biology and Life Sciences
Brain natriuretic peptide
Cardiovascular disease
Care and treatment
Clinical trials
Criminal investigation
Desaturase
Double-Blind Method
Drug dosages
Enzymes
Fatty Acid Desaturases - genetics
Fatty acids
Fatty Acids, Omega-3 - administration & dosage
Fatty Acids, Omega-3 - pharmacology
Female
Fibrosis
Galectin-3
Gene polymorphism
Genes
Genetic aspects
Genetic polymorphisms
Genomes
Genotypes
Guanine
Heart
Heart attack
Heart attacks
Hospitals
Humans
Inflammation
Linoleic acid
Linoleic Acid - blood
Lipids
Male
Medicine
Medicine and Health Sciences
Middle Aged
Myocardial infarction
Myocardial Infarction - blood
Myocardial Infarction - drug therapy
Myocardial Infarction - genetics
Natriuretic peptides
Omega 3 fatty acids
Patients
Peptides
Pharmacogenomic Variants
Polymorphism
Polymorphism, Single Nucleotide
Polyunsaturated fatty acids
Prospective Studies
Pulmonary arteries
Purines
Retirement benefits
Tertiary Care Centers
Treatment Outcome
Ventricular Remodeling - drug effects
Womens health
title 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
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