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Arterial Properties in Relation to Genetic Variations in the Adducin Subunits in a White Population

Seidlerová, Jitka ; Staessen, Jan A. ; Bochud, Murielle ; Nawrot, Tim ; Casamassima, Nunzia ; Citterio, Lorena ; Kuznetsova, Tatiana ; Jin, Yu ; Manunta, Paulo ; Richart, Tom ; Struijker-Boudier, Harry A. ; Fagard, Robert ; Filipovský, Jan ; Bianchi, Giuseppe

In: American Journal of Hypertension, 2009, vol. 22, no. 1, p. 21-26

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    Titre
    • Arterial Properties in Relation to Genetic Variations in the Adducin Subunits in a White Population
    Auteur
    • Seidlerová, Jitka. Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
    • Staessen, Jan A.. Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
    • Bochud, Murielle. Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    • Nawrot, Tim. Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
    • Casamassima, Nunzia. Divisione di Nefrologia Dialisi e Ipertensione, Ospedale San Raffaele, Dipartimento di Scienze e Tecnologie Biomediche, Universitá Vita Salute, Milan, Italy
    • Citterio, Lorena. Divisione di Nefrologia Dialisi e Ipertensione, Ospedale San Raffaele, Dipartimento di Scienze e Tecnologie Biomediche, Universitá Vita Salute, Milan, Italy
    • Kuznetsova, Tatiana. Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
    • Jin, Yu. Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
    • Manunta, Paulo. Divisione di Nefrologia Dialisi e Ipertensione, Ospedale San Raffaele, Dipartimento di Scienze e Tecnologie Biomediche, Universitá Vita Salute, Milan, Italy
    • Richart, Tom. Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
    • Struijker-Boudier, Harry A.. Department of Pharmacology and Toxicology, Cardiovascular Research Institute, University of Maastricht, Maastricht, The Netherlands
    • Fagard, Robert. Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
    • Filipovský, Jan. Faculty of Medicine in Pilsen, Charles University, Pilsen, The Czech Republic
    • Bianchi, Giuseppe. Divisione di Nefrologia Dialisi e Ipertensione, Ospedale San Raffaele, Dipartimento di Scienze e Tecnologie Biomediche, Universitá Vita Salute, Milan, Italy
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • American Journal of Hypertension, 2009, vol. 22, no. 1, p. 21-26. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:299288
    Summary
    Background Adducin is a membrane skeleton protein, which consists of either α- and β- or α- and γ-subunits. We investigated whether arterial characteristics might be related to the genes encoding ADD1 (Gly460Trp-rs4961), ADD2 (C1797T-rs4984), and ADD3 (IVS11+386A>G-rs3731566). Methods We randomly recruited 1,126 Flemish subjects (mean age, 43.8 years; 50.3% women). Using a wall-tracking ultrasound system, we measured the properties of the carotid, femoral, and brachial arteries. We studied multivariate-adjusted phenotype-genotype associations, using a population- and family-based approach. Results In single-gene analyses, brachial diameter was 0.15 mm (P = 0.0022) larger, and brachial distensibility and cross-sectional compliance were 1.55 × 10-3/kPa (P = 0.013) and 0.017 mm2/kPa (P = 0.0029) lower in ADD3 AA than ADD3 GG homozygotes with an additive effect of the G allele. In multiple-gene analyses, the association of brachial diameter and distensibility with the ADD3 G allele occurred only in ADD1 GlyGly homozygotes. Otherwise, the associations between the arterial phenotypes in the three vascular beds and the ADD1 or ADD2 polymorphisms were not significant. In family-based analyses, the multivariate-adjusted heritability was 0.52, 0.38, and 0.30 for brachial diameter, distensibility, and cross-sectional compliance, respectively (P < 0.001). There was no evidence for population stratification (0.07 ≤ P ≤ 0.96). Transmission of the mutated ADD3 G allele was associated with smaller brachial diameter in 342 informative offspring (-0.12 ± 0.04 mm; P = 0.0085) and in 209 offspring, who were ADD1 GlyGly homozygotes (-0.14 ± 0.06 mm; P = 0.018). Conclusions In ADD1 GlyGly homozygotes, the properties of the brachial artery are related to the ADD3 (A386G) polymorphism, but the underlying mechanism needs further clarification. American Journal of Hypertension (2009). doi: 10.1038/ajh.2008.261