Abstract
In the European Project on Genes in Hypertension (EPOGH), we investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C−532T and G−6A polymorphisms in the angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384 parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariables, and subjected to multivariate analyses, using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 vs 80.4 g/m2), sodium excretion (229 vs 186 mmol/day), and the prevalence of the AGT −6A (55.7 vs 40.6%) and −532T (16.8 vs 9.4%) alleles. In population-based as well as in family-based analyses, we observed positive associations of LVMI and mean wall thickness (MWT) with the −532T allele in Slavic, but not in Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were significantly higher in carriers of the −532T/−6A haplotype than in those with the −532C/−6G or −532C/−6A allele combinations. In women, LVMI was neither associated with single AGT gene variants nor with the haplotypes (0.19<P<0.98). In Slavic offspring carrying the AGT −532C/−6G or −532C/−6A haplotypes, LVMI significantly increased with higher sodium excretion (+3.5 g/m2/100 mmol; P=0.003), whereas such association was not present in −532T/−6A haplotype carriers (P-value for interaction 0.04). We found a positive association between LVMI and the AGT −532T allele due to increased MWT. This relation was observed in Slavic male offspring. It was therefore dependent on gender, age and ecogenetic context, and in addition it appeared to be modulated by the trophic effects of salt intake on LVM.
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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 sponsored 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). Genotyping was supported by research grants from the Bundesministerium for Education, Science and Technology to Eva Brand and Stefan-Martin Herrmann (BMBF 0313040A) and from the Deutsche Forschungsgemeinschaft to Stefan-Martin Herrmann (Graduierten-Kolleg 754, Myokardiale Genexpression und Funktion, Myokardhypertrophie).
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Appendix
Coordination and Committees
Project Coordinator—JA Staessen. Scientific Coordinator—K Kawecka-Jaszcz. Steering Committee—S Babeanu, E Casiglia, J Filipovsky, K Kawecka-Jaszcz, C Nachev, Y Nikitin, J Peleška, JA Staessen. Data Management Committee—T Kuznetsova, JA Staessen, K Stolarz, V Tikhonoff, J-G Wang. Publication Committee—E Casiglia, K Kawecka-Jaszcz, Y Nikitin. Advisory Committee on Molecular Biology—G Bianchi (Milan), E Brand (Berlin), SM Herrmann (Münster), HA Struijker-Boudier (Maastricht). EPOGH-EurNetGen Liaison—A Dominiczak (Glasgow), JA Staessen (Leuven).
EPOGH Centres
A complete list of the EPOGH investigators has been published in Kuznetsova et al.9
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Kuznetsova, T., Staessen, J., Reineke, T. et al. Context-dependency of the relation between left ventricular mass and AGT gene variants. J Hum Hypertens 19, 155–163 (2005). https://doi.org/10.1038/sj.jhh.1001793
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DOI: https://doi.org/10.1038/sj.jhh.1001793
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