D.S. Aprilia, Widodo, M.S. Rohman, D. Huswo, M. Lukitasari
Several experiments have identified polymorphism in the proximal of angiotensinogen (AGT). G-6A is one of polymorphism of AGT that involved hypertensive risk. This polymorphism increased AGT plasma level that may caused by increased transcription activity. This polymorphism located in proximal promoter that may regulate the gene. This polymorphism may regulated by Sp1 that influenced by polymorphism that affect angiotensinogen expression. However, the mechanism of interaction Sp1 and G-6A and its influence for expression is unknown. Thus, this study aimed to investigate the interaction between polymorphism G-6A and Sp1 (Specificity protein 1). We used molecular docking for predicting interaction and molecular dynamic for predicting the stability the interaction. We reported that the Sp1-DNA allele A complex was more stable than allele G complex. The conformation during simulation showed that the Sp1-DNA allele A complex was more stable than allele G complex. The Sp1-DNA allele A complex have more bond than allele G complex. The bond consist of hydrogen contact and hydrophobic contact that may contribute to form stable interaction in Sp1-DNA allele A complex. This study suggested that the G to A alteration at the position -6 leads to increased AGT promoter activity, that may increased risk in causing hypertension. © 2016, International Journal of Pharmaceutical and Clinical Research. All rights reserved.
Faculty of Medicine, University of Brawijaya, Malang, Indonesia; Biology Department, Faculty of Mathematics and Sciences, University of Brawijaya, Malang, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine, Brawijaya University, Saiful Anwar General Hospital, Malang, Indonesia; Nursing Department, Faculty of Medicine, University of Brawijaya, Malang, Indonesia