<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_abm-2018-0027_s_005_w2aab3b7b2b1b6b1aab1c17b1Aa"><h3>Background</h3><p>Single nucleotide polymorphism (SNP) G–152A (rs11568020) in the promoter of the angiotensinogen gene (<italic>AGT</italic>) 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.</p></sec><sec id="j_abm-2018-0027_s_006_w2aab3b7b2b1b6b1aab1c17b2Aa"><h3>Objectives</h3><p>To determine the frequency of SNP G–152A in Indonesian patients with hypertension and the function of this SNP.</p></sec><sec id="j_abm-2018-0027_s_007_w2aab3b7b2b1b6b1aab1c17b3Aa"><h3>Methods</h3><p>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.</p></sec><sec id="j_abm-2018-0027_s_008_w2aab3b7b2b1b6b1aab1c17b4Aa"><h3>Results</h3><p>The <italic>AGT</italic> 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.</p></sec><sec id="j_abm-2018-0027_s_009_w2aab3b7b2b1b6b1aab1c17b5Aa"><h3>Conclusions</h3><p>SNP G–152A reduces the favorability of binding of HIF-1 to the HRE. The occurrence of this SNP in the <italic>AGT</italic> promoter of Indonesian patients with essential hypertension suggests that the G allele is a genetic susceptibility factor in hypertension regulated by HIF-1.</p></sec></abstract>

BackgroundSingle 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.ObjectivesTo determine the frequency of SNP G–152A in Indonesian patients with hypertension and the function of this SNP.MethodsWe 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.ResultsThe 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.ConclusionsSNP 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.

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

Department of Cardiology and Vascular Medicine

Universitas Brawijaya – Saiful Anwar General Hospital

Asian Biomedicine

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

BackgroundSingle nucleotide polymorphism (SNP) G–152A (rs11568020) in the promoter of the angiotensinogen gene (AGT) may modulate its transcription....

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

Article Category: Original article

Publicado en línea: 31 dic 2018

Páginas: 15 - 25

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

Palabras clave
angiotensinogen, 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.

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

Article Category: Original article

Publicado en línea: 31 dic 2018

Páginas: 15 - 25

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

Palabras claveangiotensinogen, 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.

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