Arterial properties in relation to genetic variation in alpha-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 < or =0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm(2) 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 x 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 (P< or =0.005) in AGT CG haplotype homozygotes compared with non-carriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 x 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.
Seidlerová
J
J
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Staessen
J A
JA
Nawrot
T
T
Brand
E
E
Brand-Herrmann
S-M
SM
Casamassima
N
N
Citterio
L
L
Hasenkamp
S
S
Kuznetsova
T
T
Li
Y
Y
Manunta
P
P
Richart
T
T
Struijker-Boudier
H A
HA
Fagard
R
R
Filipovsk Ygrave
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D001530:Belgium; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000502:physiology*; D002648:Child; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics; D014463:Ultrasonography; D044465:White People / Q000235:genetics*; D055815:Young Adult; D000099291:Adducins
D000808:Angiotensinogen; D002148:Calmodulin-Binding Proteins; D044140:Receptor, Angiotensin, Type 1; D000099291:Adducins