title: Common variants associated with changes in levels of circulating free fatty acids after administration of glucose-insulin-potassium (GIK) therapy in the IMMEDIATE trial.
abstract: Glucose-insulin-potassium (GIK) therapy may promote a shift from oxygen-wasteful free fatty acid (FFA) metabolism to glycolysis, potentially reducing myocardial damage during ischemia. Genetic variation associated with FFA response to GIK was investigated in an IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) sub-study (n=117). In patients with confirmed acute coronary syndromes, associations between 132 634 variants and 12-h circulating FFA response were assessed. Between initial and 6-h measurements, three LINGO2 variants were associated with increased levels of total FFA (P-value for 2 degree of freedom test, P2df⩽5.51 × 10-7). Lead LINGO2 single-nucleotide polymorphism, rs12003487, was nominally associated with reduced 30-day ejection fraction (P2df=0.03). Several LINGO2 signals were linked to alterations in epigenetic profile and gene expression levels. Between 6 and 12 h, rs7017336 nearest to IMPA1/FABP12 showed an association with decreased saturated FFAs (P2df=5.47 × 10-7). Nearest to DUSP26, rs7464104 was associated with a decrease in unsaturated FFAs (P2df=5.51 × 10-7). Genetic variation may modify FFA response to GIK, potentially conferring less beneficial outcomes.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|School of Medicine and Pharmacology and Centre for Genetic Origins of Health and Disease (GOHaD), Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Perth, WA, Australia.
authors.forename: K L
authors.initials: KL
authors.lastname: Ellis
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Departments of Pediatrics and Genetics and Genomic Sciences, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rodriguez-Murillo
authors.affiliation: Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA.|Regulatory and Clinical Research Management, Regis College, Weston, MA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Beshansky
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Ainehsazan
authors.affiliation: Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA.
authors.forename: H P
authors.initials: HP
authors.lastname: Selker
authors.affiliation: Molecular Cardiology Research Institute Center for Translational Genomics, Tufts Medical Center, Boston, MA, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Huggins
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Cupples
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: I
authors.initials: I
authors.lastname: Peter
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002314:Cardioplegic Solutions / Q000008:administration & dosage*; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005838:Genotype; D005947:Glucose / Q000008:administration & dosage; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011188:Potassium / Q000008:administration & dosage; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002314:Cardioplegic Solutions; C534006:FABP12 protein, human; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D054639:Mitogen-Activated Protein Kinase Phosphatases; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; C500883:DUSP26 protein, human; D054637:Dual-Specificity Phosphatases; D005947:Glucose; D011188:Potassium