PubMed Health⌕ Search

Biomedical subjects

S Visvikis

Publications and source records attributed to S Visvikis.

At least 55 records · Page 3Linked to original sources
PubMed1998

Genetics strongly determines the wall thickness of the left and right carotid arteries.

In 76 supposedly healthy families, we investigated the familial resemblance of left and right carotid intima-media thickness (IMT) measured by B-mode ultrasonography and the impact of the common apolipoprotein E (apo E) polymorphism and the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE). Genetic factors accounted for about 30% of IMT variation. The insertion/deletion ACE polymorphism did not influence carotid IMT, whereas apoE polymorphism explained about 1.5% of only right carotid IMT variability independently of cholesterol levels. The apo epsilon2 and apo epsilon4 alleles were associated with lower right carotid IMT than was the apo epsilon3 allele. We conclude that genetic factors strongly contribute to IMT variability in healthy people and that the apo E polymorphism may be one of these factors.

Analysis of Variance↗
PubMed1998

Apolipoprotein E4, lipoprotein lipase C447 and angiotensin-I converting enzyme deletion alleles were not associated with increased wall thickness of carotid and femoral arteries in healthy subjects from the Stanislas cohort.

Studies have shown contrasting results concerning the relation between carotid intima-media thickness (IMT) and apolipoprotein E (apo E) and angiotensin-converting enzyme (ACE) polymorphisms. Subjects, 76 men and 74 women, between 33 and 50 years, without any history of cardiovascular disease and without any anti-hypertensive or lipid lowering medication were selected from the Stanislas cohort. The IMT of carotid and femoral arteries were investigated by B-mode ultrasonography. The common apo E, (C/G)447 lipoprotein lipase (LPL) and I/D ACE gene polymorphisms and serum ACE activity were determined. In the overall sample, male sex, age, systolic blood pressure, BMI, serum apo B level and tobacco consumption were positively correlated with carotid and femoral IMT. The common apo E polymorphism, the (C/G)LPL447 polymorphism and ACE activity were not related to carotid and femoral IMT variability in either men or women. Unexpectedly, the I allele of the ACE gene was related to higher femoral IMT than the D allele in non-smokers only. Similar results were observed after adjustment for the main covariates of IMT variability. In conclusion, amongst our young adult sample the candidate risk factors for cardiovascular disease, apo epsilon4, C447-LPL and D-ACE alleles and ACE activity were not associated with increased carotid and femoral IMT.

Adult↗
PubMed1998

Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer's patients.

Apolipoprotein D (apoD) is a member of the lipocalin family of proteins. Most members of this family are transporters of small hydrophobic ligands, although in the case of apoD, neither its physiological function(s) nor its putative ligand(s) have been unequivocally identified. In humans, apoD is expressed in several tissues, including the CNS, and its synthesis is greatly increased during regeneration of rat peripheral nerves. As apoD may have an important function in the nervous system and, particularly, in nerve regeneration, we measured immunoreactive apoD levels in the hippocampus and in CSF of patients with either Alzheimer's disease (AD) or other neuropathologies. In parallel, we determined the concentrations of apolipoprotein E (apoE), another apolipoprotein also implicated in nerve regeneration and in the etiology of AD. Levels of apoD but not apoE were increased in the hippocampus of AD patients compared with controls. ApoD concentrations, as determined by radioimmunoassay, were significantly increased in the CSF of AD patients (4.23 +/- 1.58 microg/ml) and patients with other pathologies (3.29 +/- 1.35 microg/ml) compared with those in the CSF of normal subjects (1.15 +/- 0.71 microg/ml). Although the differences were smaller than for apoD, the mean apoE concentrations in the CSF of both groups of patients were also significantly higher than those of controls. In AD patients, apoD, but not apoE, levels in CSF and hippocampus increased as a function of inheritance of the epsilon4 apoE allele. This study therefore demonstrates that increased apoD levels in the hippocampus and in CSF are a marker of neuropathology, including that associated with AD, and are independent of apoE concentrations.

Aged↗
PubMed1998

Intima-media thickness and diameter of carotid and femoral arteries in children, adolescents and adults from the Stanislas cohort: effect of age, sex, anthropometry and blood pressure.

OBJECTIVES: To study carotid and femoral intima-media thicknesses and diameters in relation to age, sex, morphologic status and blood pressure. PARTICIPANTS: The subjects were 369 men and women (aged 10-54 years) from the Stanislas cohort, with no known cardiovascular disease. METHODS: Intima-media thicknesses and diameters were measured by B-mode ultrasonography. The effects of sex, age, smoking, anthropometric variables, cholesterol and blood pressure were studied using bivariate and regression analysis. RESULTS: Carotid and femoral intima-media thicknesses were not affected by age nor by sex up to 18 years of age. Thereafter, they increased sharply in men and remained higher than in women. Values were correlated with systolic blood pressure only in men, and with fat-free mass in children and young adults only at the femoral site. Smoking, body mass index and fat mass were associated with intima-media thicknesses only in adults. Carotid diameter was little affected by age during childhood and in adults. Femoral diameter increased up to the age of 18 in both sexes and remained unaffected by age thereafter. This increase was more pronounced in boys, and so values became consistently greater in males aged over 14 years. Carotid diameter was correlated with body mass index or fat mass whereas femoral diameter was correlated with weight or fat-free-mass in children and men. The opposite was observed in women. CONCLUSION: Sex differences occur before adolescence for arterial diameter, but only at an adult age for intima-media thickness. In young subjects, carotid geometry seems to be influenced by blood pressure and excess body weight, while femoral artery geometry seems to be related to blood pressure and body growth.

Adolescent↗
PubMed1998

Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations: a family study with part of the Stanislas Cohort.

Increased plasma plasminogen activator inhibitor-1 (PAI-1) concentration has been identified as a risk factor for coronary heart disease. We investigated the relative contribution of both metabolic factors involved in the insulin resistance (IR) syndrome and polymorphisms of the PAI-1 gene to plasma levels of PAI-1 in 228 healthy nuclear white families from the Stanislas Cohort. Variables related to IR included body mass index, waist-to-hip ratio, fasting insulin, triglyceride, and HDL cholesterol. Five PAI-1 gene polymorphisms were studied, including a newly described G+12078A substitution in the 3' region. A sex difference was observed, with fathers exhibiting higher IR state and PAI-1 levels and stronger correlations between PAI-1 and IR variables than mothers. Such a difference was not observed in offspring. Family correlations were of similar magnitude for fibrinolytic parameters and IR variables. The PAI-1 genotypes A-844G, -675 4G/5G, and G+12078A polymorphisms, which were in strong linkage disequilibrium, were associated with plasma PAI-1 levels. In multivariate analysis, IR explained a major part of PAI-1 variability (49% in fathers, 29% in mothers), whereas polymorphisms had only a minor contribution, explaining 3% of variability in women and having no significant effect in men. We conclude that plasma levels of PAI-1 are, in a healthy population, primarily determined by the IR syndrome, this relationship being stronger in males. The contribution of the PAI-1 gene seems larger in females. These results deserve special attention for understanding the relationships observed between fibrinolytic parameters and the risk of developing a cardiovascular ischemic event.

Adolescent↗
PubMed1998

Objectives, design and recruitment of a familial and longitudinal cohort for studying gene-environment interactions in the field of cardiovascular risk: the Stanislas cohort.

The main objective of the Stanislas cohort is to study the role and the contribution of genetic and environmental factors to cardiovascular status. We plan: a) to describe the degree of association of a large number of cardiovascular risk indicators with cardiovascular endpoints, b) to evaluate the contribution of genetic and that of environmental factors to this association, c) to follow the evolution of these risk indicators during a period of at least ten years, d) to search for the determinants influencing this evolution. The principal variables studied are: a) blood pressure, cardiac mass, and wall thickness of carotid and femoral arteries, b) obesity and fat mass, c) indicators of lipid metabolism, d) genetic polymorphisms of several cardiovascular risk candidate genes, e) food, tobacco and alcohol consumption, f) consumption of drugs and anti-oxidant vitamins. Between September 1993 and August 1995, 1006 families consisting of the two biological parents with at least two children were recruited totalling 4295 individuals. This cohort will be followed up until 2004. There will be two health examinations five and ten years after the initial examination. A bank of blood samples (serum and plasma) in liquid nitrogen and DNA (-80 degrees C) has been established.

Adult↗
PubMed1998

DNA extraction and stability for epidemiological studies.

During the last few years, an important development of molecular biology techniques has been observed in research and clinical laboratories, and consequently the availability of DNA is becoming essential for epidemiological studies. Several DNA extraction procedures have been proposed. However as the quantity and quality of the DNA extracted is very variable, standardization of the storage of samples, and of extraction procedures becomes essential. Three steps will be considered. (i) Procedures of whole blood preservation prior to extraction which seem to affect yield and purity of the DNA extracted; (ii) DNA extraction procedures, which must be validated by a systematic DNA quality control using DNA molecular weight screening and spectrophotometric analysis, and also by verification that the DNA obtained is well adapted for molecular biology applications; (iii) the third important factor to study is the storage of DNA, since data on short-term (several months) and especially on long-term (several years) DNA stability is often missing and/or conflicting. Detailed studies must be done in order to establish guidelines for proper handling of genetic material.

DNA↗
PubMed1998

A multilocus genotyping assay for cardiovascular disease.

In our efforts to develop diagnostic tests for complex multifactorial disorders, and to assist the research community in evaluating genetic markers for predisposition to cardiovascular disease, we have developed a prototype assay to genotype up to 35 variable sites among 15 genes. The candidate markers in this panel were selected from biological pathways likely to contribute to the development and progression of cardiovascular disease. Each sample is amplified in two multiplex polymerase chain reactions that are then hybridized to an array of immobilized oligonucleotide probes. The assay has been applied to a population-based cohort representing 238 families; allele frequencies observed among 455 unrelated parents from this cohort agree with available literature values. Data from a cohort of 142 lipid-clinic patients were used to explore locus associations with arterial occlusion, as measured by quantitative angiography. This prototype assay provides a research tool for studies to assess the association of multiple markers with disease, and for clinical studies to evaluate marker association with patient responsiveness to experimental therapies.

Adult↗
PubMed1998

Association of apolipoprotein E polymorphism and concentration with serum lipids and apolipoprotein level in the Chinese from Shanghai.

The influence of apolipoprotein E polymorphism and apoE level on serum lipids and apolipoproteins was investigated in 71 healthy people and 43 patients with coronary artery disease from Shanghai. The frequency of apoE alleles was 0.06 for epsilon2, 0.86 for epsilon3, and 0.07 for epsilon4 in the healthy group, and 0.14 for epsilon2, 0.77 for epsilon3, and 0.09 for epsilon4 in the coronary artery disease group. There was no significant difference in the frequency of apoE alleles between these two groups. Serum levels of triglyceride and apo AI did not differ according to apoE genotypes, whereas serum level of apoB was significantly different according to apoE genotypes (p<0.05) both in healthy and coronary artery disease groups. However, in the healthy group, apo epsilon2 allele carriers had significantly higher level of apoE than apo epsilon3 and epsilon4 allele carriers (p<0.001) and apo epsilon4 allele carriers had significantly higher level of total cholesterol than apo epsilon3 and epsilon2 allele carriers. These were not observed in the coronary artery disease group. ApoE concentration was positively correlated with cholesterol, apoAI, and apoB levels in the control subjects and no significant correlation was observed with triglyceride level. In contrast, apoE level was positively related only to triglyceride level in the coronary artery disease group. In the control group, apoE genotypes and apoE level explained together 19.3% and 26.6% of the variability of apoB and cholesterol level, respectively, apoE polymorphism explained 23% of the variability of apoE level and apoE level explained 13.2% of the variability of apoAI level. In the coronary artery disease group, only apoE level explained 41.7% of triglyceride variability. Finally we compared our results with those previously obtained in a French healthy population, the Stanislas cohort. Results suggested that there were some difference between the Chinese control and the French subjects.

Adult↗
PubMed1998

Biological variations and genetic reference values for apolipoprotein E serum concentrations: results from the STANISLAS cohort study.

Serum apolipoprotein (apo) E concentrations were determined by immunoturbidimetry in 4284 subjects from 4 to 71 years of age and belonging to 1003 nuclear families recruited for the STANISLAS cohort study between January 1994 and August 1995. Values for apo E ranged from 16 to 169 mg/L, with a geometric mean +/- SD values of 46.6 +/- 13.8 mg/L in the overall sample. The interindividual variability varied from 24.6% to 32.0% among family members. Females exhibited higher apo E values than males until the age of 17-26 years. Conversely, after the age of 26 years, serum apo E concentrations were higher in men than in women. Biological factors affecting serum apo E concentrations were described in fathers, mothers, sons, and daughters and explained up to 32.0% of the apo E variability in daughters and 19.0% in fathers. The main biological factors affecting apo E concentrations were the following: apo E polymorphism, waist-to-hip ratio, oral contraceptive intake, puberty, body mass index, age, and gender. Given the importance of apo E polymorphism in the regulation of apo E concentrations, we recommend the use of genetic-based reference values for the clinical interpretation of serum apo E concentrations.

Adolescent↗
PubMed1997

Cerebrospinal fluid apolipoprotein E level is increased in late-onset Alzheimer's disease.

Worldwide evidence has recently shown that the allele epsilon4 of apolipoprotein E (ApoE) is a genetic risk factor for Alzheimer's disease (AD) underlining the possible role of apoE in the physiopathology of AD. To evaluate the usefulness of apoE concentration in pathogenesis of AD, we measured the cerebrospinal fluid (CSF) levels of apoE. CSF apoE level was significantly higher in 38 patients with late-onset AD than in 31 control patients and 47 patients suffering from other neurological and related diseases. Higher levels of CSF apoE were also present in a subset of patients with meningoencephalitis, motor neuron disease, and low back pain. The increase of CSF-apoE in AD is in agreement with results from studies that find an increase of mRNA apoE in the brains of AD patients. Compared to other works, these results underline the importance and the difficulties of the selection of the controls. The CSF apoE level seems to be a reflection of neuronal damage and/or an inflammatory reaction that may be common to AD and other neurological and related diseases.

Age of Onset↗
PubMed1997

High sensitivity of laser-induced fluorescence detection in capillary gel electrophoresis for accurate apolipoprotein E genotyping.

Human apolipoprotein E (apoE) is a product of a polymorphic gene. In the general population, it shows two major mutations, which lead to the appearance of three common alleles encoding for three protein isoforms. This polymorphism is important in the regulation of lipid metabolism. Accurate apoE phenotyping or genotyping has become essential in clinical laboratories, since the epsilon 4 allele has been associated with cardiovascular and Alzheimer's diseases. Endonuclease restriction isotyping, followed by slab gel electrophoresis, is a rapid and convenient method for the investigation of common apoE genotypes. However, during the large-scale apoE genotyping of the STANISLAS cohort, we were confronted with a partial lack of sensitivity and resolution power of this traditional method, which sometimes leads to the misclassification of the genotypes epsilon 2/2 and epsilon 3/2. We have overcome this difficulty by separating the restriction fragments with capillary gel electrophoresis linked to laser-induced fluorescence detection. The baseline resolution was 2 bp, and the sensitivity limit attainable was similar to that by radioactive detection. The distinction between the epsilon 3/2 and the epsilon 2/2 genotypes became unequivocal, even when only low amounts of DNA were available for amplification.

Alleles↗
PubMed1997

Combined effects of lipoprotein lipase and apolipoprotein E polymorphisms on lipid and lipoprotein levels in the Stanislas cohort.

We have genotyped 1101 supposedly healthy subjects from the Stanislas cohort for the lipoprotein lipase (LPL) gene Ser417(C)-->stop (G) polymorphism and/or for the apolipoprotein (apo)E common polymorphism. Genotypic effects of the two polymorphisms on fasting serum triglycerides (TG), total cholesterol (Tchol), high density lipoprotein-cholesterol (HDLc), low density lipoprotein-cholesterol (LDLc), apoB, apoA-I, and apoE levels were studied separately for each polymorphism and in conjunction. epsilon 4 allele and high apoE levels were associated with high levels of LDLc, Tchol, apoB, and TG. The G allele of LPL was significantly associated with low TG levels. We found a clear interaction between the LPL/apoE polymorphisms and apoE levels on serum TG variation. Total variability of TG levels in women and men of 42.31% and 53.62% respectively, were mainly explained by apoE concentration and these two polymorphisms. ApoE and LPL genes simultaneously modulated TG levels.

Adult↗
PubMed1996

Effects of apo B and apo E gene polymorphisms on lipid and apolipoprotein concentrations after a test meal.

The role of apo B signal peptide and apo E polymorphisms, and individual factors (age, sex, etc.) have been investigated on the interindividual variability of the postprandial response of 274 subjects ingesting a 1.260-KJ milkshake. The mean postprandial response, observed during 4 h, is significantly positive for total cholesterol (P < 0.005), LDL-cholesterol (P < 0.0001), triglycerides (P < 0.001), apo E (P < 0.0001) and glucose (P < 0.0001), whereas HDL-cholesterol, apo A-I and apo B do not present mean postprandial variation. Independently of the mean response, some parameters present a large interindividual variability of response, which is significantly influenced by cofactors, such as weight or BMI, for total and LDL-cholesterol, apo B and apo E or tobacco use for HDL-cholesterol. Sex has no effect on any lipid levels. Total, LDL-cholesterol and apo E responses are correlated with their corresponding fasting values. ApoB signal peptide polymorphism is not involved in the postprandial responses, whereas apo E polymorphism explains a significant part of the variability of HDL-cholesterol and apo A-I responses.

Adult↗
PubMed1996

Family study of lipoprotein lipase gene polymorphisms and plasma triglyceride levels.

To better characterize the role of the lipoprotein lipase (LPL) gene in the determination of triglyceride levels in healthy subjects, a study was performed in 193 nuclear families (384 parents, means age = 42.0 +/- 5.2 years; 399 offspring, mean age = 14.6 +/- 4.3 years) volunteering to have a free health checkup examination. The pattern of familial resemblance was compatible with a zero correlation between spouses, a weak father-offspring correlation (0.099 +/- 0.054; P < 0.07), and significant mother-offspring (0.235 +/- 0.053; P < 10(-4)) and sib-sib (0.294 +/- 0.064; P < 10(-4)) correlations. Associations of triglyceride levels with the LPL HindIII and PvuII polymorphisms were investigated by a familial measured genotype analysis, specifying sex- and age-dependent polymorphism effects. The effects associated with both polymorphisms were significant only in fathers, the H+ and P+ alleles being associated with raised triglyceride levels. The HindIII and PvuII polymorphisms explained 3.5% and 3%, respectively, of the variability of triglycerides in fathers. The relationship was weakened after prior adjustment on body mass index, but remained significant for PvuII. Because of the lack of effect in mothers and offspring, the polymorphisms did not contribute to the covariance of triglyceride levels in relatives. In conclusion, this family study showed a weak relationship of the HindIII and PvuII polymorphisms to plasma triglyceride levels in young healthy male subjects. The effects detectable only in fathers suggest a possible modulation of the LPL expression by hormonal or lifestyle factors.

Adolescent↗
PubMed1996

Frequencies of five genetic polymorphisms in coronarographed patients and effects on lipid levels in a supposedly healthy population.

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and angiographically proven coronary artery disease patients. The polymorphic candidate loci investigated were the apolipoprotein (apo) B signal peptide and XbaI polymorphism, the apo E polymorphism and two polymorphism of lipoprotein lipase (LPL) gene: Hind/III and PvuII. Apo B signal peptide and HindIII/LPL polymorphisms showed significant differences in allele partition between cases and controls; the rare alleles of both polymorphisms were less frequent (p < 0.05) in cases. We looked for associations between the polymorphisms and lipid concentration variability in a supposedly healthy population (145 men and 144 women). Apo B signal peptide, apo E and PvuII/LPL polymorphisms seem to influence some lipid metabolism parameters significantly. Apo AI and LpCIII levels were significantly different among apo B signal peptide genotypes: Del homozygotes had the highest concentrations of both variables. The epsilon 4 allele of apo E polymorphism was associated with increased concentrations of total cholesterol, LDL cholesterol and apo B. Increased LpAI:AII levels observed in E3 homozygotes (p < 0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

Adult↗
PubMed1996

Apolipoprotein E genotype epsilon 4/epsilon 2 in the STANISLAS Cohort Study--dominance of the epsilon 2 allele?

Apolipoprotein (apo) E has been discussed as a marker for cardiovascular risk, but information about lipid traits in healthy individuals having one of the rare apoE genotypes (epsilon 4/epsilon 2, epsilon 2/epsilon 2 or epsilon 4/epsilon 4) is scarce. Our work was designed to answer the following questions: 1. Are the allelic effects of epsilon 2 and epsilon 4 on lipid traits additive or dominant? 2. If there is additivity, do the allelic effects of epsilon 2 and epsilon 4 have the same magnitude? 3. Are the allelic effects neutralised in epsilon 4/ epsilon 2 individuals who are under the influence of both rare alleles? Allelic effects on apoB and apoE serum levels were codominant. Allelic models are thus not adequate to study the influence of apoE polymorphism on these traits. Allelic effects were additive for total cholesterol, LDL-C, HDL-C and apoAI, with epsilon 2 having a greater impact than epsilon 4. Serum levels differed significantly between epsilon 4/epsilon 2 and epsilon 3/epsilon 3 individuals only for apoE (p < 0.001) and for apoB (p < 0.05).

Adult↗