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Arterial properties in relation to genetic variation in α-adducin and the renin–angiotensin system in a White population


Earlier studies have demonstrated the interaction between ADD1 and ACE in relation to arterial properties. We investigated whether arterial characteristics might also be related to interactions of ADD1 with other renin–angiotensin system genes. Using a family-based sampling frame, we randomly recruited 1064 Flemish subjects (mean age, 43.6 years; 50.4% women). By means of a wall-tracking ultrasound system, we measured the properties of the carotid, femoral and brachial arteries. In multivariate-adjusted analyses, we assessed the multiple gene effects of ADD1 (Gly460Trp), AGT (C–532T and G–6A) and AT1R (A1166C). In ADD1 Trp allele carriers, but not in ADD1 GlyGly homozygotes (P-value for interaction 0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm2 kPa−1; P=0.020) in carriers of the AT1R C allele than in AT1R AA homozygotes, with a similar trend for femoral distensibility (11.3 vs 10.2 × 10−3 kPa−1; P=0.055). These associations were independent of potential confounding factors, including age. Family-based analyses confirmed these results. Brachial diameter (4.35 vs 4.18 mm) and plasma renin activity (PRA) (0.23 vs 0.14 ng ml−1 h−1) were increased (P0.005) in AGT CG haplotype homozygotes compared with non-carriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 × 10−3 kPa−1; P=0.011). There was no interaction between AGT and any other gene in relation to the measured phenotypes. ADD1 and AT1R interactively determine the elastic properties of the femoral artery. There is a single-gene effect of the AGT promoter haplotypes on brachial properties and PRA.

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This study would not have been possible without the voluntary collaboration of the participants. The municipality Hechtel-Eksel provided logistic support. We acknowledge the expert technical assistance of Sandra Covens, Linda Custers, Marie-Jeanne Jehoul, Hanne Truyens and Ya Zhu (Studies Coordinating Centre, Leuven, Belgium). The European Project on Genes in Hypertension (EPOGH) is endorsed by the European Council for Cardiovascular Research and the European Society of Hypertension. Research included in this report was supported by the European Union (grants IC15-CT98-0329-EPOGH, LSMH-CT-2006-037093 InGenious HyperCare and HEALTH-F4-2007-201550 HyperGenes); the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0424.03, G.02.56.05 and G.0575.06); the Katholieke Universiteit Leuven, Belgium (OT/00/25 and OT/05/49); the Czech Society of Hypertension; the Ministero Universitá e Ricerca Scientifica of Italy (PRIN Grant 2006065339_01); and the Else Kröner-Fresenius Stiftung (P27/05//A24/05//F01). EB is supported by a Heisenberg Professorship from the Deutsche Forschungsgemeinschaft (Br 1589/8-1).

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Seidlerová, J., Staessen, J., Nawrot, T. et al. Arterial properties in relation to genetic variation in α-adducin and the renin–angiotensin system in a White population. J Hum Hypertens 23, 55–64 (2009).

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