TY - JOUR
T1 - Genetic modifiers of response to glucose-insulin-potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial
AU - Ellis, K. L.
AU - Zhou, Y.
AU - Beshansky, J. R.
AU - Ainehsazan, E.
AU - Selker, H. P.
AU - Cupples, L. A.
AU - Huggins, G. S.
AU - Peter, I.
N1 - Publisher Copyright:
© 2015 Macmillan Publishers Limited All rights reserved.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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, P 2df ≤4.75 × 10-7) and infarct size with GIK (P 2df <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 (P 2df ≤4.26 × 10-7), but not outcomes. Gene variants may modify glucose and potassium response to GIK infusion, contributing to cardiovascular outcomes in ACS.
AB - 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, P 2df ≤4.75 × 10-7) and infarct size with GIK (P 2df <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 (P 2df ≤4.26 × 10-7), but not outcomes. Gene variants may modify glucose and potassium response to GIK infusion, contributing to cardiovascular outcomes in ACS.
UR - http://www.scopus.com/inward/record.url?scp=84947488726&partnerID=8YFLogxK
U2 - 10.1038/tpj.2015.10
DO - 10.1038/tpj.2015.10
M3 - Article
C2 - 25778467
AN - SCOPUS:84947488726
SN - 1470-269X
VL - 15
SP - 488
EP - 495
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 6
ER -