Akhiyan Hadi Susanto, Widodo, Mohammad Saifur Rohman, Didik Huswo Utomo, Mifetika Lukitasari
Background: Single nucleotide polymorphism (SNP) G–152A (rs11568020) in the promoter of the angiotensinogen gene (AGT) may modulate its transcription. Translation of mRNA to angiotensinogen induces hypertension during hypoxia. The G allele at position –152 is located within the hypoxia-response element (HRE) transcription factor-binding site for the hypoxia-inducible factor 1 (HIF-1) heterodimer. However, the function of the –152 site in HIF-1 binding is not fully elucidated. Objectives: To determine the frequency of SNP G–152A in Indonesian patients with hypertension and the function of this SNP. Methods: We determined the frequency of the SNP in 100 patients by direct sequencing, and the influence of SNP G–152A on predicted binding of HIF-1 to the HRE using a docking approach in silico. Results: The AGT promoter in our patients had genetic variants –152G and –152A (19:1). Predicted binding indicated that HIF-1 directly contacts the major groove of the G allele, but not the A allele. Scoring according to weighted sum High Ambiguity Driven biomolecular DOCKing showed that the score for the A allele–HIF-1 complex (–47.1 ± 6.9 kcal/mol) was higher than that for the G allele–HIF-1 complex (–94.6 ± 14.1 kcal/mol), indicating more favorable binding of HIF-1 to the G allele. Conclusions: SNP G–152A reduces the favorability of binding of HIF-1 to the HRE. The occurrence of this SNP in the AGT promoter of Indonesian patients with essential hypertension suggests that the G allele is a genetic susceptibility factor in hypertension regulated by HIF-1. © 2018 Sciendo. All Rights Reserved.
Basic Nursing Department, School of Nursing, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, 651445, Indonesia; Biology Department, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, 65145, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya – Saiful Anwar General Hospital, Malang, 65145, Indonesia; Medical Surgical Nursing Department, School of Nursing, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
