Analysis in silico of the single nucleotide polymorphism G–152A in the promoter of the angiotensinogen gene of Indonesian patients with essential hypertension

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.

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Analysis in silico of the single nucleotide polymorphism G–152A in the promoter of the angiotensinogen gene of Indonesian patients with essential hypertension

Akhiyan Hadi Susanto

Widodo

Mohammad Saifur Rohman

Didik Huswo Utomo

Mifetika Lukitasari

Artikel-Kategorie: Original article

Online veröffentlicht: 31. Dez. 2018

Seitenbereich: 15 - 25

DOI: https://doi.org/10.1515/abm-2018-0027

Schlüsselwörterangiotensinogen, essential hypertension, genetic promoter region, hypoxia-inducible factor 1, molecular docking, simulation, single nucleotide polymorphism

© 2018 Akhiyan Hadi Susanto et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Background

Objectives

Methods

Results

Conclusions

Schlüsselwörter
angiotensinogen, essential hypertension, genetic promoter region, hypoxia-inducible factor 1, molecular docking, simulation, single nucleotide polymorphism