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

Abstract

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 p0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm 2 kPa À1 ; P ¼ 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 Â 10 À3 kPa À1 ; P ¼ 0.055). These associations were independent of potential confounding factors, including age. Familybased analyses confirmed these results. Brachial diameter (4.35 vs 4.18 mm) and plasma renin activity (PRA) (0.23 vs 0.14 ng ml À1 h À1 ) were increased (Pp0.005) in AGT CG haplotype homozygotes compared with noncarriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 Â 10 À3 kPa À1 ; P ¼ 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.

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly

“…162 Additionally, the cytoskeleton protein alphaadducin polymorphism has been associated with excess risk among elderly patients with hypertension and CAD. 163 This polymorphism is implicated in renal sodium handling and BP regulation, 164 elastic properties of conduit arteries, 165 and hypertension, 166 as well as ischemic stroke in elderly women. 167 …”

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly

“…Additionally, the cytoskeleton protein alpha-adducin polymorphism has been associated with excess risk among elderly patients with hypertension and CAD (163). This polymorphism is implicated in renal sodium handling and BP regulation (164), elastic properties of conduit arteries (165), and hypertension (166), as well as ischemic stroke in elderly women (167). 1.5.2.3.2.…”

Do level and variability of systolic blood pressure predict arterial properties or vice versa?

“…The carotid measurements were obtained over three separate intervals of 5.2 s, which on average included 15 heart cycles. 19 Other measurements At each contact, the nurses administered the same questionnaire to collect information about the participants' medical history, smoking and drinking habits, and intake of medications. Body mass index was body weight in kilogram divided by body height in meter squared.…”