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Genetic modifiers of response to glucose–insulin–potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial

The Pharmacogenomics Journal volume 15, pages 488–495 (2015)Cite this article

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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.

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Acknowledgements

The Genetic Ancillary Study was funded by the National Institutes of Health (NIH) grant from National Heart, Lung and Blood Institute (NHLBI; R01HL090997). This work was also supported by National Center for Research Resources Grant Number UL1RR025752, now the National Center for Advancing Translational Sciences, NIH Grant Number UL1 TR000073. The IMMEDIATE trial was funded by the NIH cooperative agreement from NHLBI (U01HL077821, U01HL077823 and U01HL077826). Clinical Trial Registration: The IMMEDIATE trial is registered at www.ClinicalTrials.gov (NCT00091507).

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Authors and Affiliations

  1. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    K L Ellis, E Ainehsazan & I Peter

  2. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    Y Zhou & L A Cupples

  3. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA

    J R Beshansky

  4. Regulatory and Clinical Research Management, Regis College, Weston, MA, USA

    J R Beshansky & H P Selker

  5. Molecular Cardiology Research Institute Center for Translational Genomics, Tufts Medical Center, Boston, MA, USA

    G S Huggins

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Correspondence to I Peter.

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Ellis, K., Zhou, Y., Beshansky, J. et al. Genetic modifiers of response to glucose–insulin–potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial. Pharmacogenomics J 15, 488–495 (2015). https://doi.org/10.1038/tpj.2015.10

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