Arterial properties in relation to genetic variations in the adducin subunits in a white population.
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.
Seidlerová
Jitka
J
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Staessen
Jan A
JA
Bochud
Murielle
M
Nawrot
Tim
T
Casamassima
Nunzia
N
Citterio
Lorena
L
Kuznetsova
Tatiana
T
Jin
Yu
Y
Manunta
Paulo
P
Richart
Tom
T
Struijker-Boudier
Harry A
HA
Fagard
Robert
R
Filipovský
Jan
J
Bianchi
Giuseppe
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001530:Belgium / Q000453:epidemiology; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D002648:Child; D003598:Cytoskeletal Proteins; D004247:DNA / Q000235:genetics*; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D014463:Ultrasonography; D014655:Vascular Resistance / Q000235:genetics*; D044465:White People; D055815:Young Adult; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D004247:DNA; D000099291:Adducins