Arterial properties in relation to genetic variations in the adducin subunits in a white population.


Autoria(s): Seidlerová J.; Staessen J.A.; Bochud Murielle; Nawrot T.; Casamassima N.; Citterio L.; Kuznetsova T.; Jin Y.; Manunta P.; Richart T.; Struijker-Boudier H.A.; Fagard R.; Filipovský J.; Bianchi G.
Data(s)

2009

Resumo

BACKGROUND: Adducin is a membrane skeleton protein, which consists of either alpha- and beta- or alpha- and gamma-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 x 10(-3)/kPa (P = 0.013) and 0.017 mm(2)/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 < or = P < or = 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.

Identificador

http://serval.unil.ch/?id=serval:BIB_2F27043D31DE

isbn:1879-1905[electronic]

pmid:18787518

doi:10.1038/ajh.2008.261

isiid:000261939700008

Idioma(s)

en

Fonte

American Journal of Hypertension, vol. 22, no. 1, pp. 21-26

Palavras-Chave #Adolescent; Adult; Aged; Aged, 80 and over; Belgium/epidemiology; Brachial Artery/physiopathology; Brachial Artery/ultrasonography; Calmodulin-Binding Proteins/genetics; Carotid Arteries/physiopathology; Carotid Arteries/ultrasonography; Child; Cytoskeletal Proteins; DNA/genetics; European Continental Ancestry Group; Female; Femoral Artery/physiopathology; Femoral Artery/ultrasonography; Genetic Variation; Humans; Hypertension/ethnology; Hypertension/genetics; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Vascular Resistance/genetics; Young Adult
Tipo

info:eu-repo/semantics/article

article