The locus, 4p32.3 [MARCH1-LINC01207] showed significant risk for DM-IS (OR 5.587 [3.086–10.12]) and was located near APELA and MARCH1. APELA is a novel endogenous peptide ligand that activates the APJ receptor axis and is cardioprotective against HTN, MI, pulmonary arterial hypertension, and heart failure [37, 38]. This evidence concerns the gene APLNR and hypertensive disorder.