title: Genetic variation at glucose and insulin trait loci and response to glucose-insulin-potassium (GIK) therapy: the IMMEDIATE trial.
abstract: The mechanistic effects of intravenous glucose, insulin and potassium (GIK) in cardiac ischemia are not well understood. We conducted a genetic sub-study of the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial to explore effects of common and rare glucose and insulin-related genetic loci on initial to 6-h and 6- to 12-h change in plasma glucose and potassium. We identified 27 NOTCH2/ADAM30 and 8 C2CD4B variants conferring a 40-57% increase in glucose during the first 6 h of infusion (P<5.96 × 10(-6)). Significant associations were also found for ABCB11 and SLC30A8 single-nucleotide polymorphisms (SNPs) and glucose responses, and an SEC61A2 SNP with a potassium response to GIK. These studies identify genetic factors that may impact the metabolic response to GIK, which could influence treatment benefits in the setting of acute coronary syndromes (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, Tufts University School of Medicine, Boston, 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: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 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 / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005947:Glucose / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011188:Potassium / Q000627:therapeutic use; D040641:Quantitative Trait Loci / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium