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 XP04 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.

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes

“…A positive correlation between FUBP1 mRNA and both of the hexokinases was found in several types of cancers (Kang et al 2019 ). Variants in LCA5 gene were shown to modify glucose response in a clinical trial of insulin and potassium (GIK) infusion in acute coronary syndromes (Ellis et al 2015 ). The rs9352745 associated with GWG is an eQTL for SH3BRGL2 , whose expression is associated with diabetes (type 1, type 2 and gestational) in a meta-analysis study.…”

“The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes”

“…A positive correlation between FUBP1 mRNA and both of hexokinases was found in several types of cancers (Kang, Lee, Kim, Lee, & Kim, 2019). Variants in LCA5 gene were shown to modify glucose response in a clinical trial of insulin and potassium (GIK) infusion in acute coronary syndromes (Ellis et al, 2015). The rs9352745 associated with GWG is an eQTL for SH3BRGL2 , whose expression is associated with diabetes (type 1, type 2 and gestational) in a meta-analysis study.…”

Multivariate analysis of genome-wide data to identify potential pleiotropic genes for five major psychiatric disorders using MetaCCA

“…Therefore, SRPK2 may play some important role in the development and therapeutics of other psychiatric disorders. ARFGEF2 gene was recently recognized in children with movement disorder, severe developmental delay and microcephaly including psychiatric disorders (Ellis et al, 2015; Yilmaz et al, 2016). From a biochemistry view, the GO terms have also shown that ARFGEF2 had functional enrichment including apical recycling endosome, basolateral recycling endosome, recycling endosome, and peri-centrosomal recycling endosome.…”