title: Genetic modifiers of response to glucose-insulin-potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial.
abstract: Modifiers of response to glucose, insulin and potassium (GIK) infusion may affect clinical outcomes in acute coronary syndromes (ACS). In an Immediate Myocardial Metabolic Enhancement During Initial Assessment And Treatment In Emergency Care (IMMEDIATE) trial's sub-study (n = 318), we explored effects of 132,634 genetic variants on plasma glucose and potassium response to 12-h GIK infusion. Associations between metabolite-associated variants and infarct size (n = 84) were assessed. The 'G' allele of rs12641551, near ACSL1, as well as the 'A' allele of XPO4 rs2585897 were associated with a differential glucose response (P for 2 degrees of freedom test, P2df ⩽ 4.75 × 10(-7)) and infarct size with GIK (P2df < 0.05). Variants within or near TAS1R3, LCA5, DNAH5, PTPRG, MAGI1, PTCSC3, STRADA, AKAP12, ARFGEF2, ADCYAP1, SETX, NDRG4 and ABCB11 modified glucose response, and near CSF1/AHCYL1 potassium response (P2df ⩽ 4.26 × 10(-7)), but not outcomes. Gene variants may modify glucose and potassium response to GIK infusion, contributing to cardiovascular outcomes in ACS.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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: Institute for Clinical Research and Health Policy Studies, 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: Regulatory and Clinical Research Management, Regis College, Weston, MA, USA.
authors.forename: H P
authors.initials: HP
authors.lastname: Selker
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: 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 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 / Q000188:drug therapy* / Q000235:genetics*; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose; D011188:Potassium