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J Seidlerová,
J A Staessen,
T Nawrot,
E Brand, S-M Brand-Herrmann,
N Casamassima,
L Citterio,
S Hasenkamp,
T Kuznetsova,
Y Li,
P Manunta,
T Richart,
H A Struijker-Boudier,
R Fagard,
J Filipovsk Ygrave
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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 < 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.
Journal of Human Hypertension 10/2008; 23(1):55-64. · 2.80 Impact Factor
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J Seidlerov|[aacute,
J A Staessen,
T Nawrot,
E Brand, S-M Brand-Herrmann,
N Casamassima,
L Citterio,
S Hasenkamp,
T Kuznetsova,
Y Li,
P Manunta,
T Richart,
H A Struijker-Boudier,
R Fagard,
J Filipovsk|[ygrave
[show abstract]
[hide abstract]
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 (P0.005) 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.Keywords: arterial stiffness, arterial distensibility, α-adducin, angiotensin II type 1 receptor, angiotensinogen, clinical genetics
Journal of Human Hypertension 09/2008; 23(1):55-64. · 2.80 Impact Factor
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V Tikhonoff,
S Hasenkamp,
T Kuznetsova,
L Thijs,
Y Jin,
T Richart,
H Zhang, S-M Brand-Herrmann,
E Brand,
E Casiglia,
Ja Staessen
Journal of Human Hypertension 08/2008; 22(12):864-7. · 2.80 Impact Factor
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ABSTRACT: Adrenomedullin (ADM) is a vasodilator and inhibits salt appetite. An A-to-G substitution at position -1984 in the promoter region of the ADM gene likely increases transcription. We therefore investigated this polymorphism in relation to blood pressure and urinary sodium in a Chinese population. We genotyped 427 Chinese enrolled in a family-based population study. We measured blood pressure by conventional sphygmomanometry and ambulatory monitoring. The frequencies of the ADM AA, AG, and GG genotypes were 50.6, 38.2, and 11.2%, respectively. In adjusted analyses, G allele carriers, compared to AA homozygotes, had significantly lower conventional (45.3 versus 48.5 mm Hg, P = 0.004) and 24-h (42.6 versus 44.3 mm Hg, P = 0.03) pulse pressures and urinary sodium excretion (143.8 versus 159.4 mmol/day, P = 0.03). In parents, but not offspring, both systolic pressure and pulse pressure were significantly (P<0.01) lower in G allele carriers. The genotypic difference in sodium excretion was consistent across the age range. In 68 informative offspring, transmission of the G allele was associated with lower urinary sodium excretion (effect size, 40.1 mmol/day, P = 0.01). In 81 healthy volunteers, the plasma ADM concentration was 15.2% higher in GG homozygotes than in sex- and age-matched AA subjects (11.4 versus 9.9 pmol/l, P = 0.10). In conclusion, in Chinese, the ADM -1984G allele is associated with lower sodium excretion and in older subjects also with lower systolic pressure and narrower pulse pressure.
Kidney International 04/2006; 69(7):1153-8. · 6.61 Impact Factor
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T Kuznetsova,
J A Staessen,
T Reineke,
A Olszanecka,
A Ryabikov,
V Tikhonoff,
K Stolarz,
G Bianchi,
E Casiglia,
R Fagard, S-M Brand-Herrmann,
K Kawecka-Jaszcz,
Y Nikitin,
E Brand
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ABSTRACT: In the European Project on Genes in Hypertension (EPOGH), we investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C-532T and G-6A polymorphisms in the angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384 parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariables, and subjected to multivariate analyses, using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 vs 80.4 g/m2), sodium excretion (229 vs 186 mmol/day), and the prevalence of the AGT -6A (55.7 vs 40.6%) and -532T (16.8 vs 9.4%) alleles. In population-based as well as in family-based analyses, we observed positive associations of LVMI and mean wall thickness (MWT) with the -532T allele in Slavic, but not in Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were significantly higher in carriers of the -532T/-6A haplotype than in those with the -532C/-6G or -532C/-6A allele combinations. In women, LVMI was neither associated with single AGT gene variants nor with the haplotypes (0.19 < P <0.98). In Slavic offspring carrying the AGT -532C/-6G or -532C/-6A haplotypes, LVMI significantly increased with higher sodium excretion (+3.5 g/m2/100 mmol; P=0.003), whereas such association was not present in -532T/-6A haplotype carriers (P-value for interaction 0.04). We found a positive association between LVMI and the AGT -532T allele due to increased MWT. This relation was observed in Slavic male offspring. It was therefore dependent on gender, age and ecogenetic context, and in addition it appeared to be modulated by the trophic effects of salt intake on LVM.
Journal of Human Hypertension 03/2005; 19(2):155-63. · 2.80 Impact Factor
