Sophie Visvikis - Academia.edu (original) (raw)

Papers by Sophie Visvikis

Journal of Lipid Research, 1992

Human apolipoprotein A-IV exhibits a polymorphism, first investigated at the protein level, that ... more Human apolipoprotein A-IV exhibits a polymorphism, first investigated at the protein level, that is caused by a single amino acid substitution of glutamine to histidine at codon 360, Detection of this polymorphism requires polymerase chain reaction (PCR) and direct sequencing of the amplified products, radiolabeled allele-specific oligonucleotides (ASOs) technique, or restriction enzyme analysis of the amplified products. However, these techniques involve the use of radioactivity and/or are not well suited to the rapid processing of a large number of samples. In this paper, we propose a new technique, a bispecificallele primer amplification, in which a simple electrophoresis of

Journal of Lipid Research, 1996

The clinical relevance of apoE concentration in lipoprotein fractions should be evaluated. We inv... more The clinical relevance of apoE concentration in lipoprotein fractions should be evaluated. We investigated the impact of the common apolipoprotein (apo) E polymorphism in conjunction with very low density lipoprotein (VLDL) apoE concentration on the receptor binding properties of VLDL preparations from 17 normolipidemic subjects to the HepC2 cell surface receptors. All six apoE genotypes were studied. When apoE genotype alone was considered, two subgroups could be distinguished: VLDL without apoE isoform E2 (VLDL3/3, VLDL-3/4, and VLDL4/4) showed significantly higher affinity than VLDL with apoE2 (VLDL-4/2, VLDL-3/2, and VLDL-2/2). Once we adjusted for VLDL apoE content, we observed that VLDL affinity to HepC2 cell surface receptors decreased, according to apoE genotype, in the following order: VLDL4/4 (100%) > VLDL-3/4 (93%) > VLDL-2/2 (30%). Moreover, we found that VLDL apoE concentration could modify isoform-specific binding. An analysis in 47 subjects showed that the concentration of total VLDL protein and the VLDL apoE concentration varied considerably. The variation of VLDL apoE was independent of apoE genotype and corresponding serum apoE levels. We conclude that, in addition to apoE genotype, apoE content of VLDL is an important determinant of the receptor binding properties of VLDL.-Bohnet, K., T. Pillot, S. Visvikis, N. Sabolovic, and G. Siest. Apolipoprotein (apo) E genotype and apoE concentration determine binding of normal very low density lipoproteins to HepC2 cell surface receptors.

Drug Development Research, 2002

Annales De Biologie Clinique, 2004

Les glutathion S‐transferases (GST), enzymes polymorphes, metabolisent des xenobiotiques implique... more Les glutathion S‐transferases (GST), enzymes polymorphes, metabolisent des xenobiotiques impliques dans la survenue de pathologies comme les cancers, les maladies cardiovasculaires et respiratoires. Les variants alleliques des classes GSTM1, T1 et P1 pourraient moduler la susceptibilite individuelle a ces pathologies. Les meta‐analyses montrent que l‘allele nul GSTM1*0 est associe a une faible augmentation des cancers du poumon (OR (95 % IC) ∓ 1,17 (1,07‐1,27)), de la vessie (OR ∓ 1,44 (1,23‐1,68) et du larynx (OR ∓ 1,42 (1,10‐1,84)). Seul l‘allele nul GSTT1*0 semble etre associe a une augmentation du risque de tumeurs du cerveau (astrocytomes (OR ∓ 2,36 (1,41‐3,94) et meningiomes (OR ∓ 3,57 (1,82‐6,92)). Certains variants alleliques de la GSTP1 sont associes a une augmentation de risque de cancer de la vessie chez les fumeurs (OR ∓ 2,40 (1,12‐4,95)) et de l‘asthme (OR ∓ 3,5 (2,7‐4,6)). Enfin, le risque coronarien est augmente chez les fumeurs porteurs de l‘allele nul GSTM1*0 (OR ∓ 2,30 (1,40‐9,00)) et de l‘allele fonctionnel GSTT1*1 (OR ∓ 2,5 (1,30‐4,80)). Ce dernier est egalement associe a une augmentation du risque d‘arteriopathie des membres inferieurs (OR ∓ 3,60 (1,40‐9,00)). Ces donnees montrent que les polymorphismes des GST sont des facteurs de risque pour ces pathologies. Contrairement aux maladies cardiovasculaires, ces facteurs de risque paraissent independants de la consommation de tabac dans le cas du cancer du poumon alors qu‘ils n‘ont pas ete examines dans les autres cancers. Par consequent, d‘autres travaux sont necessaires pour etudier les interactions potentielles entre les genotypes GST et des carcinogenes chimiques, notamment ceux presents dans la fumee de tabac.

Neurobiology of Aging, 2000

Serum apolipoprotein (apo) AI concentration was studied in 98 Alzheimer's disease (AD) patients (... more Serum apolipoprotein (apo) AI concentration was studied in 98 Alzheimer's disease (AD) patients (77.56 Ϯ 8.83 years) and 59 healthy, elderly controls (75.37 Ϯ 5.27 years). ApoAI levels were significantly lower (p Ͻ 10 Ϫ7) in AD patients. An apoAI cutoff value of 1.50 g/L, could distinguish between the two groups with a sensitivity of 71% and a specificity of 69%. ApoAI levels were highly correlated with mini-mental state (MMSE) scores of patients (p Ͻ 0.0001). These relationships remained significant after adjustment for multiple testing. Our findings raise the question of the potential implication of apoAI in the etiopathology of AD and bring serum apoAI concentration to the fore as an important biochemical marker.

Stv Sang Thrombose Vaisseaux, Oct 1, 2003

Auteur(s) : Sandy Maumus, Jean-Brice Marteau, Gerard Siest, Sophie Visvikis Inserm U525, 30, rue ... more Auteur(s) : Sandy Maumus, Jean-Brice Marteau, Gerard Siest, Sophie Visvikis Inserm U525, 30, rue Lionnois, 54000 Nancy, France et Centre de medecine preventive, 2, avenue du Doyen Jacques Parisot 54501 Vandœuvre-les-Nancy, cedex 01, France La medecine que nous entrevoyons pour l'avenir est une medecine predictive qui s'appuie sur le profil genetique des patients. Son but : adapter le mode de vie au risque de developper une pathologie, mais aussi orienter le choix [...]

Atherosclerosis Supplements, 2006

Knowledge Discovery in databases (KDD) can be seen as the analysis of large sets of observational... more Knowledge Discovery in databases (KDD) can be seen as the analysis of large sets of observational data to find unsuspected relationships and to summarize the data in novel ways that may be both understandable and useful for the analyst. The relationships and summaries derived through the KDD process are referred as models or patterns [1]. Data mining is the central step of the KDD process, where algorithms are run for extracting models or patterns of interest. Methods and Data In the present view, the analyst is an expert of the data domain who is in charge of controlling the whole KDD process, mainly by interaction with the system and by iteration of some important steps of the process, such as data selection, parameter adjustment, result interpretation and validation. In a preliminary study conducted on a test biological database in the domain of mushrooms [2], satisfying and positive results have been obtained. This has led us to start the analysis of data from a real-world database, namely the STANISLAS cohort. In both experiments, we have used the Close algorithm, for extracting closed frequent patterns and association rules [3]. Patterns are sets of items that are extracted from a formal database, i.e. a boolean array of the form individuals items, where an individual may own or not a given item. A pattern is said to be frequent if the number of individuals owning the pattern is greater than a given frequency threshold. Then approximation rules can be extracted from a pattern, with a confidence measuring the proportion of individuals verifying the rule within the formal database. The STANISLAS cohort is a longitudinal study started in 1993 which is made up of 1006 caucasian families supposed to be healthy and from homogeneous origin, recruited for medical examination at the Centre for Preventive Medicine of Vandoeuvre-Les-Nancy [4]. These families are studied for exploring genotypes and intermediate phenotypes of cardiovascular diseases (CVD). CVD are multifactorial pathologies resulting from gene-gene and gene-environment interactions. There is an increasing number of studies led in the field of CVD. Many results are obtained enlightening new potential risk factors. In parallel, the volume of data generated is growing, due to the development of leading technologies (like multiplex technologies or microarrays) coupled with studies involving big populations. Facing this huge volume of data, new kinds of data analysis methods are required, such as symbolic data mining methods, in order to determine disease susceptibility profiles. The collected information being at our disposal can be either qualitative or quantitative, and it is of many type: - environmental data : personal past history, life habits,... - clinical data : bodymass index, height, weight, blood pressure... - biological data related to risk factors : lipids and apolipoproteins (apo) such as concentration of total cholesterol, triglycerides, HDL and LDL cholesterol, apoB, apoE..., concentration of ACE, cellular adhesion molecules, and inflammation molecules - genetic data corresponding to gene polymorphisms related to cardiovascular diseases, and dealing for instance with lipids metabolism, blood pressure, or inflammation. Results In our first experiments, we have chosen to work on a subset of data from the STANISLAS cohort that has already been studied, and has given results with classical statistical analysis previously published in [5]. Briefly, the subset concerns 772 men and 780 premenopausal women, unrelated genetically, without any treatment that could interfere with cardiovascular physiopathology. For practical reasons, we have chosen to work on concentration of LDL-cholesterol (LDL-C) in mmol/L, genetic polymorphisms of apolipoprotein (apo) E and apo B that has proven to be associated with LDL-C in the Pallaud's study, and common risk factors used in this kind of study, e.g. age, sex, alcohol consumption (g/day), smoking, body mass index (kg/m2), use of oral contraceptive. The extracted rules and patterns are in agreement with the knowledge of the analyst and with the literature. In this way, we have have obtained two types of results : 1) Already known results. For example, we have done a projection on people with genotype 4/4 for the apo E polymorphism. An extracted rule states that 19 of the 25 individuals who are apo E 4/4 have their LDL concentration that exceeds the norm established by the National Cholesterol Education Program (LDL concentration must be smaller or equal to 1.60 g/l (inferior 3.44 mmol/l)). This rule is in accordance with the knowledge of the analyst and with published results [6]. 2) New results. For instance, the interpretation of an interesting rule has led us to invest the genotype distributions in a subset of our population. This study has given to us significant statistical results, never published in the literature to our knowledge. Other results of the same kind have been found, and further…

Genome Research, 1999

A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial g... more A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial genetic risk component. Consequently, techniques are needed to facilitate evaluation of complex genetic risk factors in large cohorts. We have designed a prototype assay for genotyping a panel of 35 biallelic sites that represent variation within 15 genes from biochemical pathways implicated in the development and progression of cardiovascular disease. Each DNA sample is amplified using two multiplex polymerase chain reactions, and the alleles are genotyped simultaneously using an array of immobilized, sequence-specific oligonucleotide probes. This multilocus assay was applied to two types of cohorts. Population frequencies for the markers were estimated using 496 unrelated individuals from a family-based cohort, and the observed values were consistent with previous reports. Linkage disequilibrium between consecutive pairs of markers within theapoCIII, LPL, and ELAM genes was also estimat...

Genetic Epidemiology, 1994

Plasma apolipoprotein (apo) A-IV concentration was determined by immunoelectrophoretic assay (EIA... more Plasma apolipoprotein (apo) A-IV concentration was determined by immunoelectrophoretic assay (EIA) in 119 nuclear families. No significant effect of con

FEBS Letters, 1986

Major disturbances of the lipoproteins in Tangier serum have been investigated using electrophore... more Major disturbances of the lipoproteins in Tangier serum have been investigated using electrophoretic and immunochemical techniques. Previously described anomalies concerning the striking deficiency in HDL and the very low levels of apo A-I and apo A-II in Tangier patients are illustrated and explained. Anomalies concerning the fast LDL of Tangier serum are attributed to different forms of apo B not previously described. These data are strengthened by the features of a 2-dimensional electrophoresis method elaborated in the laboratory which allows apoproteins to separate in the second dimension. These apoproteins are obtained by the delipidation of the lipoproteins fractionated in a first polyacrylamide discontinuous gel. This method clearly shows the distribution of apoproteins in the first lipoprotein track and is in perfect accordance with the new concept of lipoprotein particles.

Diabetes, 1991

We studied the molecular characteristics of three naturally occurring variants in the human apoli... more We studied the molecular characteristics of three naturally occurring variants in the human apolipoprotein B (apoB) signal peptide, their frequencies in non-insulin-dependent diabetic and random populations, and their association with several measures of lipid and carbohydrate metabolism. In a random sample of 197 French whites, there were two common alleles, 5'(JSP-24 and 5'pSP-27, with frequencies of 0.35 and 0.65, respectively. In a random sample of 181 Mexican Americans, there was an additional allele, 5'pSP-29, with a frequency of 0.03. DNA sequence analysis indicated that the signal peptide alleles consisted of the following: 5'(JSP-29 encoded 29 amino acids in the signal peptide containing two copies of the sequence CTG GCG CTG encoding Leu-Ala-Leu and a consecutive run of eight Leu-encoding condons; 5'f3SP-27 encoded 27 amino acids with a run of only six Leu condons; 5'pSP-24 encoded 24 amino acids and contained a single copy of CTG GCG CTG and a run of six Leu codons. In the sample of French whites, average apoAl and glucose levels were significantly different among signal peptide genotypes. 5'pSP-24/24 homozygotes had higher apoAl levels than the two other signal peptide genotypes (1.59 vs. 1.42 g/L, respectively). Heterozygous 5'pSP-24/27 individuals had the highest glucose levels. In the random sample of Mexican Americans, average glucose levels were also significantly different among signal peptide genotypes. However, the rank order of average glucose levels was not the same between the two samples. In the sample of Mexican Americans, glucose levels were significantly elevated (6.14 mM) in the 5'pSP-24/24

Clinical Genetics, 2008

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and... more 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 &amp;lt; 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 &amp;lt; 0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

Clinical Chemistry and Laboratory Medicine, 2003

Clinical Chemistry and Laboratory Medicine, 1998

During the last few years, an important development of molecular biology techniques has been obse... more 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 lon...

Clinical and Experimental Pharmacology and Physiology, 2001

1. The aim of the present study was to investigate carotid intima-media thickness (CIMT) in relat... more 1. The aim of the present study was to investigate carotid intima-media thickness (CIMT) in relation to anthropometric, environmental and genetic factors, as well as cholesterol and blood pressure levels. 2. The study sample was composed of 89 families, with no documented cardiovascular disease, consisting of 369 subjects (aged from 10 to 54 years) from the Stanislas cohort. 3. Carotid intima-media thickness was measured by B-mode ultrasonography. Fifteen genetic markers, including genes involved in lipid metabolism, the regulation of blood pressure, thrombosis, platelet function and endothelial cell adhesion, were studied by multiplex assay. 4. The effects of gender, age, smoking, alcohol, body mass index, cholesterol, blood pressure and genetic factors were studied using ANOVA and bivariate and regression analyses. 5. Segregation analysis was also performed to estimate the contribution of genetic and environmental factors to CIMT variability. 6. Carotid intima-media thickness values were not affected by age or by gender up to 18 years of age. Thereafter, CIMT values increased sharply in men and remained significantly higher than in women. 7. Approximately 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in the apolipoprotein CIII, cholesteryl ester transfer protein, methylene tetrahydrofolate reductase and fibrinogen genes were observed and explained approximately 20% of CIMT variation in men. 8. In women, none of the studied polymorphisms was associated with CIMT variation. 9. Our study gives new perspectives for understanding CIMT variability in healthy middle-aged subjects.