Abstract
The 825T allele of the G-protein β3-subunit is associated with increased intracellular signalling. Its association with hypertension is inconsistent. We, therefore, studied the C825T polymorphism in relation to ambulatory blood pressure as well as left ventricular structure and function in two European populations. We genotyped 248 parents and 318 offspring, enrolled in the European Project on Genes in Hypertension in Cracow, Poland (n=286) and in Novosibirsk, Russian Federation (n=280). The 24-h ambulatory blood pressure was recorded using oscillometric SpaceLabs 90207 monitors. Within each centre, a single observer performed two-dimensionally guided M-mode echocardiography and Doppler sonography to measure left ventricular structure (American Society of Echocardiography conventions) and diastolic function: early (E) and late (A) peak diastolic inflow velocities. We used analysis of covariance and generalized estimating equations to allow for covariables and nonindependence among related subjects. Genotype frequencies were similar (P=0.25) in Cracow and Novosibirsk and amounted to 44.7% for CC, 47.2% for CT, and 8.1% for TT. Among parents (mean age: 51.3 years)—but not among offspring (mean age 25.1 years)—24-h, daytime and night time systolic blood pressures were 5–6 mmHg higher in TT homozygotes than in C allele carriers. In TT homozygous parents (−8.2 cm/sec, P=0.004) as well as in TT homozygous offspring (−7.5 cm/sec, P=0.02), the E-wave was significantly reduced, which in offspring also resulted in a lower E/A ratio (–0.25, P=0.002). Neither in parents nor in offspring, left ventricular mass index was associated with the C825T polymorphism. In conclusion, in TT homozygotes of both generations, early left ventricular relaxation was reduced. In TT homozygous parents, the latter observation might be because of the higher systolic pressure associated with the TT genotype.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Farfel Z, Bourne HR, Iiri T . The expanding spectrum of G protein diseases. N Engl J Med 1999; 340: 1012–1020.
Siffert W et al. Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J Cin Invest 1995; 96: 759–766.
Zeltner R et al. G-protein β3-subunit gene (GNB3) 825T allele is associated with enhanced renal perfusion in early hypertension. Hypertension 2001; 37: 882–886.
Rosskopf D, Busch S, Manthey I, Siffert W . G-protein β3 gene: structure, prompter, and additional polymorphism. Hypertension 2000; 36: 33–41.
de la Sierra A et al. Erythrocyte ion fluxes in essential hypertensive patients with left ventricular hypertrophy. Circulation 1993; 88: 1628–1633.
Siffert W, Naber C, Walla M, Ritz E . G protein β3-subunit 825T allele and its potential association with obesity in hypertensive individuals. J Hypertens 1999; 17: 1095–1098.
Siffert W . G protein β3-subunit 825T allele, hypertension, obesity and diabetic nephropathy. Nephrol Dial Transplant 2000; 15: 1298–1306.
Siffert W et al. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J Am Soc Nephrol 1999; 10: 1921–1930.
Kuznetsova T et al. Quality control of the blood pressure phenotype in the European Project on Genes in Hypertension. Blood Press Monit 2002; 7: 215–224.
Staessen JA et al. Renal function is inversely correlated with lead exposure. N Engl J Med 1992; 327: 151–156.
Staessen JA et al. Renal function and historical environmental cadmium pollution from zinc smelters. Lancet 1994; 343: 1523–1527.
41st World Medical Assembly. Declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. Bull Pan Am Health Organ 1990; 24: 606–609.
Petrie JC, O'Brien ET, Littler WA, de Swiet M . Recommendations on blood pressure measurement by a working party of the British Hypertension Society. BMJ 1989; 293: 611–615.
van Ittersum FJ, Ijzerman RG, Stehouwer CDA, Donker AJM . Analysis of twenty-four-hour ambulatory blood pressure monitoring: what time period to assess blood pressure during walking and sleeping. J Hypertens 1995; 13: 1053–1058.
Du Bois D, Du Bois EF . A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916; 17: 863–871.
Sahn DJ, DeMaria A, Kisslo J, Weyman A . Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072–1083.
Schiller NB et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms. J Am Soc Echocardiogr 1989; 2: 358–367.
Devereux RB et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57: 450–458.
Quinones MA et al. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 2002; 15: 167–184.
Levine MA et al. Molecular cloning of beta 3 subunit, a third form of the G protein beta-subunit polypeptide. Proc Natl Acad Sci USA 1990; 87: 2329–2333.
Siffert W et al. Association of a human G-protein β 3 variant with hypertension. Nat Genet 1998; 18: 45–48.
Brand E et al. The 825C/T polymorphism of the G-protein subunit β3 is not related to hypertension. Hypertension 1999; 33: 1175–1178.
Kleinbaum DG, Kupper LL, Muller KE . Applied Regression Analysis and Other Multivariate Methods, 2nd edn. PWS-Kent Publishing Company: Boston, MA, USA, 1988, 575pp.
The SAS Institute. The GENMOD Procedure. SAS Online Doc Version 7.1: SAS/STAT. The SAS Institute Inc.: Cary, NC, USA. 2000, pp 1311–1411.
Jacobi J et al. 825 T allele of the G-protein β3 subunit gene (GNB3) is associated with impaired left ventricular diastolic filling in essential hypertension. J Hypertens 1999; 17: 1457–1562.
Poch E et al. G-protein β3 subunit gene variant and left ventricular hypertrophy in essential hypertension. Hypertension 2000; 35 (Part 2): 214–215.
Semplicini A et al. G protein β3 subunit gene 825T allele is associated with increased left ventricular mass in young subjects with mild hypertension. Am J Hypertens 2001; 14: 1191–1195.
Sedlacek K et al. Relation of the G protein β3-subunit polymorphism with left ventricle structure and function. Hypertension 2002; 40: 162–167.
Inouye I et al. Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension. Am J Cardiol 1984; 53: 120–126.
Barry WH, Bridge JHB . Intracellular calcium homeostasis in cardiac myocytes. Circulation 1993; 87: 1806–1815.
Koss KL, Kranias EG . Phospholamban: A prominent regulator of myocardial contractility. Circ Res 1996; 79: 1059–1063.
Molenaar P et al. Both beta-2 and beta-1 adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of Fallot infants, consistent with selective coupling of beta-2 adrenergic receptors to Gs-protein. Circulation 2000; 102: 1814–1821.
Li L et al. Phosphorylation of phospholamban and troponin I in beta-adrenergic induced acceleration of cardiac relaxation. Am J Physiol 2000; 278: 769H–779H.
Kauman A et al. Activation of beta-2 adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I and C protein in ventricular myocardium from patients with terminal heart failure. Circulation 1999; 99: 65–72.
Morgan JP . Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 1991; 325: 625–632.
Kobilka B, Hoffmann BB . Molecular characterization and regulation of adrenergic receptors. In: Laragh JH, Brenner BM (eds). Hypertension. Pathophysiology, Diagnosis and Management, Vol. 1, Raven Press: New York, USA, 1995, pp 841–861.
Xiao RP . Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins. Sci STKE 2001; 2001: RE15.
Xiao RP et al. Recent advances in cardiac beta2-adrenergic signal transduction. Circulation Res 1999; 85: 1092–1100.
Schunkert H et al. Association between a polymorphism in the G protein β3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension 1998; 32: 510–513.
Benjafield AV et al. G protein β3 subunit gene (GNB3) variant in causation of essential hypertension. Hypertension 1998; 32: 1094–1097.
Hengstenberg C et al. Association between polymorphism in the G protein β3 subunit gene (GNB3) with arterial hypertension but not with myocardial infarction. Cardiovasc Res 2001; 49: 820–827.
Dong Y et al. Association between the C825T polymorphism of the G protein β3-subunit gene and hypertension in Blacks. Hypertension 1999; 34: 1193–1196.
Beige J, Hohenbleicher H, Distler A, Sharma AM . The G-protein subunit β3 C825T variant and ambulatory blood pressure on essential hypertension. Hypertension 1999; 33: 1049–1051.
Kato N et al. G protein β3 subunit variant and essential hypertension in Japanese. Hypertension 1998; 32: 935–938.
Ishikawa K et al. Human G-protein β3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure. Am J Hypertens 2000; 13: 140–145.
Larson N, Hutchinson R, Boerwinkle E . Lack of association of 3 functional gene variants with hypertension in African Americans. Hypertension 2000; 35: 1297–1300.
Hegele RA et al. G protein β3 subunit gene variant and blood pressure variation in Canadian Oji-Cree. Hypertension 1998; 32: 688–692.
Hegele RA, Anderson C, Young TK, Connelly PW . G-protein β3 subunit gene splice variant and body fat distribution in Nuvavut Inuit. Genome Res 1999; 9: 972–977.
Turner ST, Schwartz GL, Chapman AB, Boerwinkle E . C825T polymorphism of the G protein β3-subunit and antihypertensive response to a thiazide diuretic. Hypertension 2001; 37: 739–743.
Acknowledgements
The European Project on Genes in Hypertension was supported by the European Union (contract numbers IC15-CT98-0329-EPOGH and QLG1-CT-2000-01137-EURNETGEN). The study was also supported by a special research grant (Onderzoekstoelage OT/99/28) from the Katholieke Universiteit Leuven (Leuven, Belgium), and by the Internationale Wetenschappelijke en Technologische Samenwerking Polen-Vlaanderen (contract number BIL 00/18).
Author information
Authors and Affiliations
Consortia
Corresponding author
Appendix
Appendix
Coordination and committees
Project Coordinator—J A Staessen.
Scientific Coordinator—K Kawecka-Jaszcz.
Steering Committee—S Babeanu (Romania), E Casiglia (Italy), J Filipovsky (Czech Republic), K Kawecka-Jaszcz (Poland), C Nachev (Bulgaria), Y Nikitin (Russian Federation), J Peles̃ka (Czech Republic), J A Staessen (Belgium).
Data Management Committee—T Kuznetsova, J A Staessen, J G Wang.
Publication Committee—E Casiglia, K Kawecka-Jaszcz, Y Nikitin.
Advisory Committee on Molecular Biology—G Bianchi (Milan), E Brand (Berlin), S M Herrmann (Berlin), H A Struijker-Boudier (Maastricht).
EPOGH-EurNetGen Liaison—A Dominiczak (Glasgow), J A Staessen (Leuven).
EPOGH centres
Belgium (Hechtel-Eksel)—E Balkestein, R Bollen, H Celis, E Den Hond, L De Pauw, P Drent, D Emelianov, R Fagard, J Gąsowski, L Gijsbers, A Hermans, T Nawrot, L Thijs, Y Toremans, J A Staessen, S Van Hulle, J G Wang, R Wolfs.
Bulgaria (Sofia)—C Nachev, A Postadjian, E Prokopova, E Shipkovenska, K Vitljanova.
Czech Republic (Pilzen)—J Filipovsky, V Svobodova, M Ticha.
Czech Republic (Prague)—O Beran, L Golán, T Grus, J Peles̃ka, Z Marecková.
Italy (Padova)—E Casiglia, A Pizzioli, V Tikhonoff.
Poland (Cracow)—K Kawecka-Jaszcz, T Grodzicki, K Stolarz, B Wizner, A Olszanecka, A Adamkiewicz-Piejko, W Lubaszewski, J Życzkowska, W Wojciechowska, M Cwynar.
Romania (Bucharest)—S Babeanu, D Jianu, C Sandu, D State, M Udrea.
Russian Federation (Novosibirsk)—Y Nikitin, S Malyutina, T Kuznetsova, E Pello, A Ryabikov, M Ryabikov, M Voevoda.
Laboratories
DNA extraction and genotyping—E Brand, SM Herrmann (Universitätklinikum Benjamin Franklin, Freie Universität Berlin, Germany); C Barlassina, G Bianchi, L Tizzoni (Divisione di Nefrologia Dialisi e Ipertensione, Ospedale San Raffaele, Dipartimento di Scienze e Tecnologie Biomediche, Universitá degli Studi di Milano, Italy); P Schiffers, H Struijker-Boudier (Vakgroep Farmacologie en Toxicologie, University of Maastricht, The Netherlands); M Voevoda (Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia).
Lithium clearance measurement—M Burnier, M Maillard (Division of Hypertension and Vascular Medicine, CHUV, University Hospital, Lausanne, Switzerland).
Rights and permissions
About this article
Cite this article
Olszanecka, A., Kawecka-Jaszcz, K., Kuznetsova, T. et al. Ambulatory blood pressure and left ventricular structure and function in relation to the G-protein β3-subunit polymorphism C825T in White Europeans. J Hum Hypertens 17, 325–332 (2003). https://doi.org/10.1038/sj.jhh.1001551
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.jhh.1001551
Keywords
This article is cited by
-
G-Protein β3-Subunit Gene C825T Polymorphism and Cardiovascular Risk: An Updated Review
High Blood Pressure & Cardiovascular Prevention (2015)
-
Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study
BMC Medical Genetics (2009)
-
GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate
Journal of Human Hypertension (2004)
-
Cardiovascular diseases and G-protein β3 subunit gene (GNB3) in the era of genomewide scans
Journal of Human Hypertension (2003)