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F Soubrier

Publications and source records attributed to F Soubrier.

At least 91 records · Page 5Linked to original sources
PubMed1994

The enigma of pseudohypoaldosteronism.

The syndrome of primary pseudohypoaldosteronism (PHA) is a hereditary disease characterized by increased aldosterone secretion associated with clinical signs of hypoaldosteronism. These include salt wasting and failure to thrive in the newborn, high urinary sodium, hyponatremia, hyperkalemia, and metabolic acidosis. Plasma renin activity is usually elevated in association with aldosterone. The clinical manifestation of the disease is variable, including severely affected patients who may die in infancy and patients who are asymptomatic. The disease seems to result from a cellular resistance to mineralocorticoid action, which could be either generalized, or restricted to the kidney. The condition is inherited as an autosomal dominant or an autosomal recessive trait; however, sporadic cases have been described. In this paper we report a 20-year follow-up study of a French family affected by PHA and we discuss the pathogenesis of the disease.

Aldosterone↗
PubMed1994

Angiotensin I converting enzyme gene: regulation, polymorphism and implications in cardiovascular diseases.

Angiotensin I converting enzyme (ACE), also called dipeptidyl-carboxypeptidase I (DCP I), is a zinc metallopeptidase widely distributed on the surface of endothelial and epithelial cells. Its role in the vasoactive peptide, the metabolism of the two active peptides, angiotensin and bradykinin, and the beneficial effects of its inhibition in cardiovascular diseases, have raised considerable interest in this enzyme. The potential implications of ACE gene polymorphism, which affects the expression of the gene in cardiovascular diseases, has been widely investigated. This review summarizes the results of these studies.

Gene Expression Regulation, Enzymologic↗
PubMed1994

The angiotensin I-converting enzyme gene polymorphism: implication in hypertension and myocardial infarction.

The angiotensin I-converting enzyme gene is one of the major genes of the renin-angiotensin and kallikrein-kinin systems and is a candidate gene for several cardiovascular diseases for which a genetic predisposition has been established. Based on analysis of the level of the enzyme in plasma, a genetic polymorphism of its expression has been well characterized. Use of a DNA marker on the angiotensin I-converting enzyme gene has shown that the gene polymorphism is located within the angiotensin I-converting enzyme gene itself. This review summarizes the results of various studies of this polymorphism in cardiovascular diseases and the hypotheses that can be proposed to explain this effect.

Animals↗
PubMed1994

Genetic basis of hypertension.

Recent advances in the genetics of hypertension include studies on localizations of many loci involved in blood pressure regulation in the rat, elucidation of the molecular mechanisms underlying monogenetic forms of hypertension, and studies of candidate genes in primary hypertension. Evidence that the angiotensinogen gene is involved in primary hypertension has been found by linkage in affected sibling pairs, and by the demonstration of increased risk of disease associated with DNA variants of the gene. Similar evidence of linkage and association has been found in preeclampsia, which suggests that the two diseases share at least one common factor of genetic susceptibility.

Angiotensinogen↗
PubMed1994

Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension.

We conducted the present study to determine whether the angiotensin II type I receptor (AT1) gene might be implicated in human essential hypertension by using case-control and linkage studies. The entire coding and 3' untranslated regions of the AT1 receptor gene (2.2 kb) were amplified by polymerase chain reaction and submitted to single-strand conformation polymorphism in 60 hypertensive subjects with a familial susceptibility. We identified five polymorphisms (T573-->C, A1062-->G, A1166-->C, G1517-->T, and A1878-->G). However, no mutations that alter the encoded amino acid sequence were detected. A case-control study performed on white hypertensive (n = 206; blood pressure, 168 +/- 16/103 +/- 9 mm Hg) and normotensive (n = 298; blood pressure, 122 +/- 10/75 +/- 9 mm Hg) subjects using three of five polymorphisms showed a significant increase in allelic frequency of C1166 in hypertensive subjects (0.36 versus 0.28 for normotensive subjects, chi 2 = 6.8, P < .01). Frequencies for the alleles of the other two polymorphisms (T573-->C, A1878-->G) were similar in both groups. We performed a linkage study using the affected sib pair method and a highly polymorphic marker of the AT1 receptor gene. There was no evidence for linkage in 267 sib pairs analyzed from 138 pedigrees. These findings would be compatible with a common variant of the AT1 receptor imparting a small effect on blood pressure; further studies will be needed to address this possibility.

Adult↗
PubMed1994

No alteration in the primary structure of the mineralocorticoid receptor in a family with pseudohypoaldosteronism.

We have studied the molecular structure of the mineralocorticoid receptor (MR) complementary DNA (cDNA) in a kindred affected by pseudohypoaldosteronism (PHA). In this family, the clinical symptoms included salt wasting and failure to thrive, accompanied by high urinary levels of sodium despite hyponatremia, hyperkalemia and metabolic acidosis, elevation of PRA, and high plasma aldosterone levels. The patients were resistant to mineralocorticoid administration, but their symptoms ameliorated after a period of sodium supplementation, which was discontinued in older patients. Binding studies performed on mononuclear leukocytes of the members of the family have shown the absence of MR in two siblings and a marked reduction in another sibling of the father, suggesting either the absence of MR or a defect of the ligand-binding domain of the MR in these patients. Southern analysis of patient's DNA did not show any major rearrangement of the MR gene. To search for point mutations in the cDNA of the MR, we performed amplification of the MR cDNA by the polymerase chain reaction and direct sequencing of amplified products. No mutation was found in the entire coding sequence of the MR in patients affected by PHA. Although these results do not exclude a molecular abnormality present on the MR gene, they indicate that PHA in this family is not related to a modification of the MR primary structure.

Aldosterone↗
PubMed1994

HYPERGENE: a clinical and genetic database for genetic analysis of human hypertension.

OBJECTIVE: Genetic studies of essential human hypertension require the recording and management of numerous data concerning multiple hypertensive families. The present paper describes a new family database, HYPERGENE, and demonstrates its potential usefulness in such a complex disease. METHODS: The database was implemented on an Apple Macintosh computer using the 4TH DIMENSION software program. Through a user-friendly interface, it offers a high-quality data record, easy data retrieval and compatibility with other software. PATIENTS: HYPERGENE contains a prospective collection of 187 families with at least two hypertensive sibs (826 subjects). Each subject was analysed according to the same protocol. To allow definition of clinical and biological phenotypes and genetic analysis, clinical and biological data were recorded and, at the same time, plasma, urine and DNA libraries were stored. RESULTS: Probands were 50.6 years old with an early onset (39.1 years of age) of hypertension (157.7/97.8 mmHg); 125 had moderate-to-severe hypertension. According to our selection criteria, only one out of 187 sibships had familial dislipidaemic hypertension. Of the living fathers, 45% were examined, and 54% of the living mothers: 48.6% had an onset of hypertension before age 50 years. Children (mean age 28.7 years) of hypertensive sibs presented a high percentage of hypertension (8.3%). CONCLUSION: The HYPERGENE database facilitates data storage and analysis on familial hypertension, and should prove a useful tool for assessing molecular biology results in the field of hypertension and for allowing collaborative research.

Adolescent↗
PubMed1994

[From positional cloning to gene identification and its function in genetic diseases].

The huge development of genetic tools, together with the availability of powerful computers have enabled the mapping of several loci responsible for genetic diseases by the positional cloning technique, also called reverse genetics. The step consisting of identifying the gene itself remains a difficult step and the function of the gene identified may remain difficult to establish. In this chapter, we will examine the various steps allowing the identification of the gene, techniques allowing the creation of animal models of human diseases and the recent progresses of these techniques.

Animals↗
PubMed1994

Short report: HYPERGENE: a clinical and genetic database for genetic analysis of human hypertension.

OBJECTIVE: Genetic studies of essential human hypertension require the recording and management of numerous data concerning multiple hypertensive families. The present report describes a new family database, HYPERGENE, and demonstrates its potential usefulness in such a complex disease. METHODS: The database was implemented on an Apple Macintosh computer using the 4TH DIMENSION software program. Through a user-friendly interface, it offers a high-quality data record, easy data retrieval and compatibility with other software. PATIENTS: HYPERGENE contains a prospective collection of 187 families with at least two hypertensive sibs (826 subjects). Each subject was analysed according to the same protocol. To allow definition of clinical and biological phenotypes and genetic analysis, clinical and biological data were recorded and, at the same time, plasma, urine and DNA libraries were stored. RESULTS: Probands were 50.6 years old with an early onset (39.1 years of age) of hypertension (157.7/97.8 mmHg); 125 had moderate-to-severe hypertension. According to our selection criteria, only one out of 187 sibships had familial dislipidaemic hypertension. Of the living fathers, 45% were examined, and 54% of the living mothers: 48.6% had an onset of hypertension before age 50 years. Children (mean age 28.7 years) of hypertensive sibs presented a high percentage of hypertension (8.3%). CONCLUSION: The HYPERGENE database facilitates data storage and analysis on familial hypertension, and should prove a useful tool for assessing molecular biology results in the field of hypertension and for allowing collaborative research.

Adult↗
PubMed1994

Role and identification of the genes involved in human hypertension.

Variance of blood pressure in the normal population is composed of environmental influences and the cumulative effects of gene structure polymorphisms. Essential hypertension results from the combined influence of these components, whose respective importance can vary considerably from individual to individual. In the rare forms of hypertension due to a single gene abnormality, the environmental component is negligible and the genetic component is represented by a major transmitted gene abnormality with major effects on the phenotype. These rare forms of monogenic hypertension offer interesting models for the study of the genes involved in essential hypertension. The angiotensinogen gene represents the first example of a strongly supported implication of a gene in essential hypertension. The success of this strategy allows the possibility of identifying other genes in essential hypertension.

Angiotensinogen↗
PubMed1993

Functional analysis of the human somatic angiotensin I-converting enzyme gene promoter.

Angiotensin I-converting enzyme (ACE) is a key enzyme in the regulation of systemic blood pressure and plays a major role in the renin-angiotensin and bradykinin-kinin systems, at the luminal surface of the vascular endothelia. To identify the promoter region, the transcription regulatory elements and the cell specificity of the ACE gene, five successive DNA deletions of the 5' upstream region (-1214, -754, -472, -343, -132 bp relative to the start site of transcription) were isolated and fused in sense and antisense orientations to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene in the promoterless plasmid pBLCAT3. Promoter activities were measured in transient transfection assays using three different cell lines from rabbit endothelium (RE), human embryocarcinoma (Tera-1) and hepatocarcinoma cells (HepG2). All five fragments of the ACE promoter region directed expression of the CAT gene when transfected into the endothelial and the embryocarcinoma cells, which contain endogenous ACE mRNA and express ACE activity. In contrast only minimal levels of promoter activity were obtained on transfection into hepatocarcinoma cells in which endogenous ACE mRNA and ACE activity were not detected. Transfection of RE and Tera-1 cells demonstrated that promoter activity was defined by the length of the ACE promoter sequence inserted into the construct. The 132 bases located upstream from the transcription start site were sufficient to confer ACE promoter activity, whereas the sequences upstream from -472 bp and between -343 bp and -132 bp were responsible for a decrease of promoter activity. Furthermore, the minimal 132 bp of the ACE promoter contains elements which direct cell-specific CAT expression. In addition, the DNA transfection study in the presence of dexamethasone suggested that the potential glucocorticoid regulatory elements, located in the sequence of the ACE promoter, are not functional.

Angiotensin I↗
PubMed1993

Genetic determinants of diastolic and pulse pressure map to different loci in Lyon hypertensive rats.

Several genetic loci involved in blood pressure regulation have recently been localized in experimental models of hypertension, but the manner in which they influence blood pressure remains unknown. Here, we report a study of the Lyon hypertensive rat strain showing that different loci are involved in the regulation of steady-state (diastolic pressure) and pulsatile (systolic-diastolic, or pulse pressure) components of blood pressure. Significant linkage was established between diastolic blood pressure and a microsatellite marker of the renin gene (REN) on rat chromosome 13, and between pulse pressure and the carboxypeptidase B gene (CPB) on chromosome 2. These findings show that two independent loci influence different haemodynamic components of blood pressure, and that pulse pressure has a specific genetic determination.

Analysis of Variance↗
PubMed1993

The angiotensin I converting enzyme gene and predisposition to high blood pressure.

Phenotypic abnormalities of the renin-angiotensin system have been associated with the predisposition to high blood pressure. The angiotensin I converting enzyme (ACE) gene has been implicated as a candidate gene. We examined the distribution of common alleles of the ACE gene and measured circulating components of the renin-angiotensin system and urinary sodium excretion in 170 young Caucasian adults with contrasting genetic predisposition to high blood pressure. Predisposition was defined on the basis of personal and parental blood pressure levels by using the four corners sampling method. Young adults with greatest predisposition who had high blood pressure and two parents with high blood pressure did not show any significant difference in the distribution of the markers of the ACE gene, either as genotype or allele frequencies, when compared with young adults with least predisposition who had low blood pressure and two parents with low blood pressure. Offspring with urinary sodium excretion above the median (143.4 mmol per day) also showed no significant differences in the distribution of ACE alleles or genotype between groups. Different genotypes were associated with different average serum ACE concentrations (p < 0.0001), but plasma angiotensin II and aldosterone showed no significant variation with ACE genotype. These results suggest that in a group of Caucasians selected from the general population, the ACE gene is not associated with genetic predisposition to high blood pressure. In this population common ACE gene allelic markers would not be useful indexes of susceptibility to hypertension.

Adult↗