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Genetic variation at glucose and insulin trait loci and response to glucose–insulin–potassium (GIK) therapy: the IMMEDIATE trial

The Pharmacogenomics Journal volume 15, pages 55–62 (2015)Cite this article

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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).

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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).

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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, Y Yang & 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, Tufts University School of Medicine, Boston, MA, USA

    J R Beshansky & H P Selker

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

    G S Huggins

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  1. K L Ellis
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Correspondence to I Peter.

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Ellis, K., Zhou, Y., Beshansky, J. et al. Genetic variation at glucose and insulin trait loci and response to glucose–insulin–potassium (GIK) therapy: the IMMEDIATE trial. Pharmacogenomics J 15, 55–62 (2015). https://doi.org/10.1038/tpj.2014.41

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