This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmieder, R. E. Articles by Regitz-Zagrosek, V. Search for Related Content PubMed PubMed Citation Articles by Schmieder, R. E. Articles by Regitz-Zagrosek, V.

CLINICAL STUDY: HYPERTENSION

Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans

Roland E. Schmieder, MD, FACC^*, Jeanette Erdmann, PhD, Christian Delles, MD^*, Johannes Jacobi, MD^*, Eckart Fleck, MD, Karl Hilgers, MD^* and Vera Regitz-Zagrosek, MD

^* Department of Medicine IV/Nephrology, University of Erlangen-Nürnberg, Nürnberg, Germany
Department of Internal Medicine and Cardiology, Charité, Campus Virchow-Klinikum, Humboldt University and Deutsches Herzzentrum Berlin, Berlin, Germany

Manuscript received October 14, 1999; revised manuscript received July 13, 2000, accepted September 11, 2000.

Reprint requests and correspondence: Dr. Roland E. Schmieder, Department of Medicine IV, University Erlangen-Nürnberg, Breslauer Str. 201, 90471 Nürnberg, Germany
Roland.Schmieder{at}rzmail.uni-erlangen.de

OBJECTIVES

Our study goal was to analyze whether gene variants of angiotensin II type 2-receptor (AT₂-R) modulate the effects of angiotensin II on the left ventricle (LV).

BACKGROUND

Experimental data suggest that angiotensin II modifies ventricular growth responses via angiotensin II type 1-receptors (AT₁-R) and AT₂-R.

METHODS

In 120 white, young male subjects with normal or mildly elevated blood pressure, we assessed plasma angiotensin II and aldosterone concentrations (RIA), 24-h urinary sodium excretion, 24-h ambulatory blood pressure and LV structure (two-dimensional guided M-mode echocardiography). The intronic +1675 G/A polymorphism of the X-chromosomal located AT₂-R gene was investigated by single-strand conformational polymorphism analysis and DNA-sequencing.

RESULTS

Hypertensive subjects with the A-allele had a greater LV posterior (11.0 ± 1.3 vs. 9.9 ± 1.3 mm, p < 0.001), septal (11.8 ± 1.4 vs. 10.1 ± 1.2 mm, p < 0.001) and relative wall thickness (0.44 ± 0.06 vs. 0.39 ± 0.06, p < 0.01) as well as LV mass index (138 ± 23 vs. 120 ± 13 g/m², p < 0.001) than those with the G-allele. Confounding factors (i.e., body mass index and surface area, plasma angiotensin II, sodium excretion, systolic and diastolic ambulatory blood pressure) were similar between the two genotypes. In normotensive subjects, relative wall thickness (0.36 ± 0.05 vs. 0.35 ± 0.05) and LV mass index (115 ± 21 vs. 112 ± 17 g/m²) were nearly identical across the two genotypes, with similar confounding variables.

CONCLUSIONS

Our data indicate that the X-chromosomal located +1675 G/A-polymorphism of the AT₂-R gene is associated with LV structure in young male humans with early structural changes of the heart due to arterial hypertension.

Abbreviations and Acronyms   AT1-R = angiotensin II type 1-receptor   AT2-R = angiotensin II type 2-receptor   BP = blood pressure   LV = left ventricle   PCR = polymerase chain reaction   RAS = renin angiotensin system

This article has been cited by other articles:

				B. Ponnuchamy and R. A. Khalil Cellular mediators of renal vascular dysfunction in hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1001 - R1018. [Abstract] [Full Text] [PDF]

				L. Pilote, K. Dasgupta, V. Guru, K. H. Humphries, J. McGrath, C. Norris, D. Rabi, J. Tremblay, A. Alamian, T. Barnett, et al. A comprehensive view of sex-specific issues related to cardiovascular disease Can. Med. Assoc. J., March 13, 2007; 176(6): S1 - S44. [Abstract] [Full Text] [PDF]

				R. E. Schmieder The role of non-haemodynamic factors of the genesis of LVH Nephrol. Dial. Transplant., December 1, 2005; 20(12): 2610 - 2612. [Full Text] [PDF]

				C. Warnecke, P. Mugrauer, D. Surder, J. Erdmann, C. Schubert, and V. Regitz-Zagrosek Intronic ANG II type 2 receptor gene polymorphism 1675 G/A modulates receptor protein expression but not mRNA splicing Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1729 - R1735. [Abstract] [Full Text] [PDF]

				K. Alfakih, R. A. Lawrance, A. Maqbool, K. Walters, S. G. Ball, A. J. Balmforth, and A. S. Hall The clinical significance of a common, functional, X-linked angiotensin II type 2-receptor gene polymorphism (-1332 G/A) in a cohort of 509 families with premature coronary artery disease Eur. Heart J., March 2, 2005; 26(6): 584 - 589. [Abstract] [Full Text] [PDF]

				T. Kuznetsova, J. A. Staessen, L. Thijs, C. Kunath, A. Olszanecka, A. Ryabikov, V. Tikhonoff, K. Stolarz, G. Bianchi, E. Casiglia, et al. Left Ventricular Mass in Relation to Genetic Variation in Angiotensin II Receptors, Renin System Genes, and Sodium Excretion Circulation, October 26, 2004; 110(17): 2644 - 2650. [Abstract] [Full Text] [PDF]

				M. P. Schneider, A. U. Klingbeil, C. Delles, M. Ludwig, R. E. Kolloch, M. Krekler, K. O. Stumpe, and R. E. Schmieder Effect of Irbesartan Versus Atenolol on Left Ventricular Mass and Voltage: Results of the CardioVascular Irbesartan Project Hypertension, July 1, 2004; 44(1): 61 - 66. [Abstract] [Full Text] [PDF]

				K. Alfakih, A. Maqbool, M. Sivananthan, K. Walters, G. Bainbridge, J. Ridgway, A. J. Balmforth, and A. S. Hall Left Ventricle Mass Index and the Common, Functional, X-Linked Angiotensin II Type-2 Receptor Gene Polymorphism (-1332 G/A) in Patients With Systemic Hypertension Hypertension, June 1, 2004; 43(6): 1189 - 1194. [Abstract] [Full Text] [PDF]

				A. Jones, S. S. Dhamrait, J. R. Payne, E. Hawe, P. Li, I. S. Toor, L. Luong, P. T.E. Wootton, G. J. Miller, S. E. Humphries, et al. Genetic Variants of Angiotensin II Receptors and Cardiovascular Risk in Hypertension Hypertension, October 1, 2003; 42(4): 500 - 506. [Abstract] [Full Text] [PDF]

				S.-M. Herrmann, V. Nicaud, K. Schmidt-Petersen, J. Pfeifer, J. Erdmann, T. McDonagh, H. J. Dargie, M. Paul, and V. Regitz-Zagrosek Angiotensin II type 2 receptor gene polymorphism and cardiovascular phenotypes: the GLAECO and GLAOLD studies Eur J Heart Fail, December 1, 2002; 4(6): 707 - 712. [Abstract] [Full Text] [PDF]

				K. F. Hilgers and J. F. E. Mann ACE Inhibitors versus AT1 Receptor Antagonists in Patients with Chronic Renal Disease J. Am. Soc. Nephrol., April 1, 2002; 13(4): 1100 - 1108. [Full Text] [PDF]

				J. Deinum, J. M.G. van Gool, M. J.M. Kofflard, F. J. ten Cate, and A.H. J. Danser Angiotensin II Type 2 Receptors and Cardiac Hypertrophy in Women With Hypertrophic Cardiomyopathy Hypertension, December 1, 2001; 38(6): 1278 - 1281. [Abstract] [Full Text] [PDF]

				C. Delles, J. Erdmann, J. Jacobi, K. F. Hilgers, E. Fleck, V. Regitz-Zagrosek, and R. E. Schmieder Aldosterone synthase (CYP11B2) -344 C/T polymorphism is associated with left ventricular structure in human arterial hypertension J. Am. Coll. Cardiol., March 1, 2001; 37(3): 878 - 884. [Abstract] [Full Text] [PDF]