학술논문

Arterial properties in relation to genetic variation in α-adducin and the renin–angiotensin system in a White population.
Document Type
Article
Source
Journal of Human Hypertension. Jan2009, Vol. 23 Issue 1, p55-64. 10p. 6 Charts, 1 Graph.
Subject
*ANGIOTENSINS
*ASPARTIC proteinases
*CAROTID artery
*HYPERTENSION
*THERAPEUTICS
*GENETIC research
Language
ISSN
0950-9240
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 0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm2 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 × 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0.005) in AGT CG haplotype homozygotes compared with non-carriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 × 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.Journal of Human Hypertension (2009) 23, 55–64; doi:10.1038/jhh.2008.113; published online 18 September 2008 [ABSTRACT FROM AUTHOR]