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 α- and β- or α- and γ-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 × 10-3/kPa (P = 0.013) and 0.017 mm2/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 ≤ P ≤ 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. American Journal of Hypertension (2009). doi: 10.1038/ajh.2008.26

Heritability and intrafamilial aggregation of arterial characteristics

BACKGROUND: We investigated the heritability and familial aggregation of various indexes of arterial stiffness and wave reflection and we partitioned the phenotypic correlation between these traits into shared genetic and environmental components. METHODS: Using a family-based population sample, we recruited 204 parents (mean age, 51.7 years) and 290 offspring (29.4 years) from the population in Cracow, Poland (62 families), Hechtel-Eksel, Belgium (36), and Pilsen, the Czech Republic (50). We measured peripheral pulse pressure (PPp) sphygmomanometrically at the brachial artery; central pulse pressure (PPc), the peripheral augmentation indexes (PAIxs) and central augmentation indexes (CAIxs) by applanation tonometry at the radial artery; and aortic pulse wave velocity (PWV) by tonometry or ultrasound. In multivariate-adjusted analyses, we used the ASSOC and PROC GENMOD procedures as implemented in SAGE and SAS, respectively. RESULTS: We found significant heritability for PAIx, CAIx, PPc and mean arterial pressure ranging from 0.37 to 0.41; P &lt;/= 0.0001. The method of intrafamilial concordance confirmed these results; intrafamilial correlation coefficients were significant for all arterial indexes (r &gt;/= 0.12; P &lt;/= 0.02) with the exception of PPc (r = -0.007; P = 0.90) in parent-offspring pairs. The sib-sib correlations were also significant for CAIx (r = 0.22; P = 0.001). The genetic correlation between PWV and the other arterial indexes were significant (rhoG &gt;/= 0.29; P &lt; 0.0001). The corresponding environmental correlations were only significantly positive for PPp (rhoE = 0.10, P = 0.03). CONCLUSION: The observation of significant intrafamilial concordance and heritability of various indexes of arterial stiffness as well as the genetic correlations among arterial phenotypes strongly support the search for shared genetic determinants underlying these traits

Interactive Influence of Genetic Effects and Effects of External Environment on Properties of Large Arteries in Relation to Sodium Management

In line with Guyton's work, the goal of our research was to explore in three European populations whether the properties of large arteries are associated with renal sodium handling, which itself changes with environmental factors and with variation in a large number of genes. Before engaging in the genetic analyses proper, we first studied the familial aggregation and the heritability of arterial properties. In all our analyses, we accounted for relatedness among participants and for covariables and confounders. In a first study, we compared the arterial characteristics and blood pressure (BP) in normotensive offspring of two normotensive parents (OFF/NT) and normotensive offspring, who had at least one hypertensive parent (OFF/HT). We measured peripheral pulse pressure (PPp) by conventional and 24-h ambulatory BP. A SphygmoCor device was used to determine the central (CAIx) and peripheral (PAIx) augmentation indexes, central pulse pressure (PPc), and aortic pulse wave velocity (aPWV). Compared with OFF/NT (n=59; 16 to 34 years of age), the OFF/HT (n=174; 17 to 40 years) had higher (0.14<P<0.0007) BP and PPp on conventional measurement (121/75 vs. 114/71 mm Hg and 46 vs. 42 mm Hg) as well as on 24-h ambulatory monitoring (118/70 vs. 114/67 mm Hg and 48 vs. 47 mm Hg). OFF/HT, compared with OFF/NT, also had..

Interactive Influence of Genetic Effects and Effects of External Environment on Properties of Large Arteries in Relation to Sodium Management

In line with Guyton's work, the goal of our research was to explore in three European populations whether the properties of large arteries are associated with renal sodium handling, which itself changes with environmental factors and with variation in a large number of genes. Before engaging in the genetic analyses proper, we first studied the familial aggregation and the heritability of arterial properties. In all our analyses, we accounted for relatedness among participants and for covariables and confounders. In a first study, we compared the arterial characteristics and blood pressure (BP) in normotensive offspring of two normotensive parents (OFF/NT) and normotensive offspring, who had at least one hypertensive parent (OFF/HT). We measured peripheral pulse pressure (PPp) by conventional and 24-h ambulatory BP. A SphygmoCor device was used to determine the central (CAIx) and peripheral (PAIx) augmentation indexes, central pulse pressure (PPc), and aortic pulse wave velocity (aPWV). Compared with OFF/NT (n=59; 16 to 34 years of age), the OFF/HT (n=174; 17 to 40 years) had higher (0.14<P<0.0007) BP and PPp on conventional measurement (121/75 vs. 114/71 mm Hg and 46 vs. 42 mm Hg) as well as on 24-h ambulatory monitoring (118/70 vs. 114/67 mm Hg and 48 vs. 47 mm Hg). OFF/HT, compared with OFF/NT, also had..

Social psychological predictors of satisfaction with intrapartum and postpartum care – what matters to women in Czech maternity hospitals?

Objective: To identify the social psychological factors affecting women’s evaluation of care provided in Czech maternity hospitals using following criteria: satisfaction with intrapartum and postpartum care, willingness to return to a given hospital and to recommend the hospital to others

Soluble RAGEs and cardiovascular risk factors in adult offspring of patients with premature coronary heart disease

Purpose: Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidant compounds which can potentiate microvascular and macrovascular complications through the formation of irreversible cross-links between molecules in the basal membrane and also by engaging the receptor for AGEs (RAGE). Soluble receptor for AGEs (sRAGE) is suggested to have a protective role neutralizing the toxic action of AGEs. We aimed to investigate differences in plasma levels of sRAGE alongside with classic cardiovascular risk factors between offspring of patients with early onset of coronary heart disease (CHD) and healthy controls. Materials and methods: In a cross-sectional design, we examined 114 adult offspring of patients with premature CHD and 194 controls. Concentrations of soluble RAGE were quantified by ELISA methods. Aortic PWV was measured using Sphygmocor device. Multivariate logistic regressions were used to compare differences between the offspring and controls. Results: In the offspring group there were more men (p = 0.023), both groups had similar age (28.5 vs. 28.9 years; p = 0.51). After adjustment for covariates, we observed significantly higher aPWV (6.17 vs. 5.82 m s−1; p = 0.001) and lower sRAGE (1308.11 vs. 1475.59; p = 0.009) in the offspring group compared to controls. The significant determinants of the intergroup difference were sRAGE (p = 0.0017), aPWV (p = 0.011) and current smoking (p = 0.0053). Conclusion: Offspring of patients with early onset of CHD compared to age-matched healthy controls had significantly lower sRAGE levels suggesting a shift in the oxidative balance between stressors and defence mechanisms that may influence a higher cardiovascular risk in the future. The measurement of sRAGE might be a valuable predictor for more precise stratification of cardiovascular risk

Long-term relationship between unattended automated blood pressure and auscultatory BP measurements in hypertensive patients

Aims: Unattended automated office blood pressure (uAutoOBP) has attracted more attention since SPRINT trial had been published. However, its long-term relationship to attended office blood pressure (AuscOBP) is not known. Material and methods: Stable treated hypertensive subjects were examined in four Czech academic hypertension centers. All subjects attended four clinical visits three months apart. uAutoOBP was measured with the BP Tru device; AuscOBP was measured three times with auscultatory method by the physician. 24-hour ambulatory blood pressure monitoring (ABPM) was performed within one week from the second clinical visit. Results: Data on 112 subjects aged 65.6 ± 10.8 years with mean AuscOBP 128.2 ± 12.2/78.5 ± 10.3 mm Hg are reported. Across the four clinical visits, the uAutoOBP was by 10.1/3.7 mm Hg lower than AuscOBP and the mean difference was similar during all four visits (P≥.061). Both uAutoOBP and AuscOBP had similar intra-individual variability during study follow-up as demonstrated by similar intraclass correlation coefficients (ICC, for systolic ICC = 0.50, for diastolic ICC = 0.72). However, the intra-individual variability of the systolic AuscOBP and uAutoOBP difference was high as demonstrated by low ICCs for absolute (ICC = 0.17 [95%CI, 0.09 – 0.25]) and low κ coefficients for categorized differences (κ ≤ 0.16). The main determinant of AuscOBP-uAutoOBP difference was AuscOBP level. The AuscOBP-uAutoOBP difference was poor tool to identify hypertension control categories defined on the basis of AuscOBP and ABPM. Conclusions: Although mean AuscOBP-uAutoOBP differences were relatively similar across the four clinical visits, intra-individual variability of this difference was high. The AuscOBP-uAutoOBP difference was poor tool to identify hypertension control categories defined on the basis of AuscOBP and ABPM. Therefore, uAutoOBP cannot be used as a replacement for ABPM

A novel nonsense mutation in the β-subunit of the epithelial sodium channel causing Liddle syndrome

Purpose Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes coding of the epithelial sodium channel – SCNN1A, SCNN1B and SCNN1G. It is characterised by early onset of hypertension and variable biochemical features such as hypokalaemia and low plasma concentrations of renin and aldosterone. Phenotypic variability is large and, therefore, LS is probably underdiagnosed. Our objective was to examine a family suspected from Liddle syndrome including genetic testing and evaluate clinical and biochemical features of affected family members. Materials and methods Thirteen probands from the Czech family, related by blood, underwent physical examination, laboratory tests, and genetic testing. Alleles of SCNN1B and SCNN1G genes were examined by PCR amplification and Sanger sequencing of amplicons. Results We identified a novel mutation in the β-subunit of an epithelial sodium channel coded by the SCNN1B gene, causing the nonsense mutation in the protein sequence p.Tyr604*. This mutation was detected in 7 members of the family. The mutation carriers differed in the severity of hypertension and hypokalaemia which appeared only after diuretics in most of them; low aldosterone level (< 0.12 nmol/l) was, however, present in all. Conclusions This finding expands the spectrum of known mutations causing Liddle syndrome. Hypoaldosteronemia was 100% sensitive sign in the mutation carriers. Low levels are observed especially in the Caucasian population reaching 96% sensitivity. Assessment of plasma aldosterone concentration is helpful for differential diagnosis of arterial hypertension. CONDENSED ABSTRACT Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes encoding the epithelial sodium channel’s α-, β- and γ-subunit. It is usually manifested by early onset of hypertension accompanied by low potassium and aldosterone levels. We performed a physical examination, laboratory tests and genetic screening in 13 members of a Czech family. We found a new mutation of the SCNN1B gene which encodes the β-subunit of the epithelial sodium channel. We describe the variability of each family member phenotype and point out the relevance of using aldosterone levels as a high sensitivity marker of Liddle syndrome in Caucasians