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Ambulatory blood pressure and left ventricular structure and function in relation to the G-protein β3-subunit polymorphism C825T in White Europeans

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.

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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).

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Correspondence to J A Staessen.

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).

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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

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