REN C-5312T, but not C-5434T, correlates to increase serum angiotensin I level in angiotensin II receptor blockers-treated hypertensive patients

Authors

  • Mohammad Saifur Rohman Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Brawijaya /Saiful Anwar General Hospital, Malang
  • Frastiqa Fahrany Biomedical Science, Faculty of Medicine, University of Brawijaya
  • Imama Maslahah Biomedical Science, Faculty of Medicine, University of Brawijaya
  • - Widodo Biology Department, Faculty of Mathematics and Sciences, University of Brawijaya
  • Mifetika Lukitasari Nursing Science, Faculty of Medicine, University of Brawijaya
  • Aditya Kurniawan Biology Department, Faculty of Mathematics and Sciences, University of Brawijaya http://orcid.org/0000-0002-9349-5916
  • Agustina Tri Endharti Parasitology Department, Faculty of Medicine, University of Brawijaya

DOI:

https://doi.org/10.3329/bjp.v11i2.25818

Keywords:

Angiotensin I receptor blocker, Angiotensin II receptor blocker, Hypertension, REN C-5312T, REN C-5434T

Abstract

Renin distal enhancer plays a crucial role in regulating renin gene (REN) expression. REN C-5312T enhancer polymorphism increased enhancer activity. REN C-5434T was also identified which supposed to part of enhancer region. Therefore, this study aimed to investigate contribution of both C-5312T and C-5434T to serum angiotensin I in response to angiotensin II receptor blockers (ARB). C-5312T was identified in 46 hypertensive patients by using multiplex polymerase chain reaction (PCR), while C-5434T by using PCR-restiction fragment length of polymorphism (RFLP). Angiotensin I was measured using enzyme linked immunosorbent assay (ELISA). A significant difference of baseline angiotensin I was observed between -5312CC and -5312CT/TT (p=0.038) as well as the angiotensin I after 5 months of ARB treatment (p=0.008) in -5434CT/TT population, but not REN C-5434T. In conclusion, C-5312T resulted in increased mRNA renin level as consequence of higher enhancer activity not only at the baseline but also after 5 months ARB treatment.

Downloads

Download data is not yet available.
Abstract
218
Download
87 Read
133

References

Cagnoni F, Njwe CAN, Zaninelli A, Ricci AR, Dafra D, DOspina A, Preti P, Destro M. Blocking RAAS at different levels: An update on the use of the direct renin inhibitors alone and in combination. Vasc Health Risk Manag. 2010; 6: 549-59.

Castrop H, Hocherl K, Kurtz A, Schweda F, Todorov V, Wagner C. Physiology of kidney renin. Physiol Rev. 2010; 90: 607-73.

Chen L, Soomi K, Eisner C, Oppermann M, Huang Y, Mizel D, Li L, Chen M, Lopez MLS, Weinstein LS, Gomez RA, Schnermann J, Briggs JP. Stimulation of renin secretion by angiotensin II blockade is Gs?-dependent. J Am Soc Nephrol. 2010; 21: 986-92.

Fuchs S, Philippe, J, Germain S, Mathieu F, Jeunemaitre X, Corvol P, Pinet F. Functionality of two new polymorphisms in the human renin gene enhancer region. J Hypertens. 2002; 20: 239198.

Germain S, Bonnet F, Philippe J, Fuchs S, Corvol P, Pinet F. A novel distal enhancer confers chorionic expression on the humanrenin gene. J Biol Chem. 1998; 273: 25292300.

Guang C, Philips RD, Jiang B, Milani F. Three key proteases- angiotensin-I-convertingenzyme (ACE), ACE2 and renin- within and beyondthe renin-angiotensin system. Arch Cardiovasc Dis. 2012; 105: 373-85.

Konoshita T, Kato N, Fuchs S.,Mizuno S, Aoyama C, Motomura M, Makino M, Wakahara S, Inoki I, Miyamori I, Pinet F. Genetic variant of the renin-angiotensin system and diabetes influences blood pressure response to angiotensin receptor blockers. Diabetes Care. 2009; 32: 1485-90.

Konoshita T, Nakaya T, Sakai A, Yamada M, Ichikawa M, Sato S, Imagawa M, Fujii M, Yamamoto K, Makino Y, Arakawa K, Suzuki J, Ishizuka T. Determinants of plasma renin activity: Role of a human renin gene variant as a genetic factor. Medicine. 2014; 93: e354.

Lukitasari M, Rohman MS, Hendrawan D. Achievement of blood pressure target with angiotensin blockage based therapy in outpatient clinic. 5th scientific meeting of Indonesian Society of Hypertension Abstract Book, 2011.

Makino Y, Konoshita T, Omori A, Maegawa N, Nakaya T, Ichikawa M, Yamamoto K, Wakahara S, Ishizuka T, Onoe T, Nakamura H. A genetic variant in the distal enhancer region of the human renin gene affects renin expression. PLoS ONE. 2015; 10: e0137469.

Mancia G, De Backer G, Dominiczak A, Cifkova, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HAJS, Zanchetti A. Guidelines for the management of arterial hypertension: The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007; 25: 110587.

Maslahah I, Rohman MS, Widodo N, Endharti AT, Utomo D. Genetic variant of C-5434T REN enhancer on serum renin levels and binding pattern of signal transducers and activators transcription 3. Int J Hypertens. 2015, 2015.

Rohman MS, Satiti IAD, Widodo N, Lukitasari M, Sujuti H. Genetic variants of C-5312T REN increased renin levels and diastolic blood pressure response to angiotensin receptor blockers. Int J Hypertens. 2015, 2015.

Santos PCJL, Krieger JE, Pereira AC. Renin-angiotensin system, hypertension, and chronic kidney disease: Pharmacogenetic implications. J Pharmacol Sci. 2012; 120: 77-88.

Additional Files

Published

2016-05-16

How to Cite

Rohman, M. S., F. Fahrany, I. Maslahah, .-. Widodo, M. Lukitasari, A. Kurniawan, and A. T. Endharti. “REN C-5312T, But Not C-5434T, Correlates to Increase Serum Angiotensin I Level in Angiotensin II Receptor Blockers-Treated Hypertensive Patients”. Bangladesh Journal of Pharmacology, vol. 11, no. 2, May 2016, pp. 552-7, doi:10.3329/bjp.v11i2.25818.

Issue

Section

Research Articles