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Biomedical subjects

Sophie Visvikis

Publications and source records attributed to Sophie Visvikis.

At least 19 recordsLinked to original sources
PubMed2003

Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD (P=0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE epsilon 4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.

Alzheimer Disease↗
PubMed2003

Homo- and hetero-complexes of exchangeable apolipoproteins in solution and in lipid-bound form.

The self-association state of human plasma apolipoprotein E (apoE) in solution and in complexes with dimyristoylphosphatidylcholine (DMPC) varying in stoichiometry was studied in sub-micromolar concentration range by gel filtration, fluorescence anisotropy, fluorescence quenching and energy transfer measurements with apolipoprotein labeled with lysine-specific fluorescent dyes. Together, these results confirm the equilibrium scheme for various apoE structures in solution: oligomer (in aged preparations) <==> 'closed' tetramer <==> 'open' tetramer ('molten globule' state) <==> native or partially denatured monomer <==> fully denatured monomer. Within DMPC:apoE discoidal complex (125:1) the apolipoprotein association state seems to be intermediate between that in solution and in larger vesicular complex (1000:1); for both complexes, the degree of exposure of fluorescein chromophores into water phase decreased. Hetero-associates of apoA-I and apoC-III-1 in solution and in the complexes with DMPC appear to behave similarly to apoE. When extrapolated to native HDL particles, 'molten globule' state seems to be a structure responsible for the interaction of exchangeable apolipoproteins with phospholipid. For a first time, the location of various apolipoprotein molecules on disc periphery was confirmed. The lysine residue(s) seems to locate closely to reacting residue(s) within apolipoprotein molecules in associates, however, with different package constraints for discoidal versus vesicular complexes with phospholipid.

Apolipoproteins↗
PubMed2003

Effect of six candidate genes on early aging in a French population.

BACKGROUND AND AIMS: The objective of this study was to examine the association between an aging indicator previously defined from a nationwide population study, and lipids and apolipoproteins, angiotensin converting enzyme, paraoxonase activities, and six candidate genes related to the aging process. METHODS: Two hundred and fifty-six healthy Caucasian men (69.8 +/- 4.0 years) were included in the study. Total cholesterol, triglycerides, HDL-cholesterol, lipoprotein(a), apolipoprotein A1, B and E concentrations, and the activities of paraoxonase, arylesterase, and angiotensin-converting enzymes were determined by standardized laboratory methods. A multiplex assay was used to genotype the studied polymorphisms: apolipoprotein E, lipoprotein lipase, paraoxonase, methylenetetrahydrofolate reductase, cystathionine beta-synthase and angiotensin-converting enzymes. RESULTS: Paraoxonase polymorphism at codon 192 (Gln/Arg) was the only one significantly associated with the aging indicator, Gln homozygotes being more advanced in aging compared with Arg allele carriers. It was also observed that the aging indicator was positively correlated with serum concentrations of total cholesterol, triglycerides and apolipoprotein B, and negatively with the activities of basal and stimulated paraoxonase and arylesterase. Multiple regression analysis showed that triglycerides and basal paraoxonase activity explain 13.6% of the variance of the aging indicator. CONCLUSIONS: Triglyceride concentration and paraoxonase gene and activities may contribute to the aging process. Taking into account the smallness of the sample size, and the poor level of significance due to the im-plication of paraoxonase polymorphism at codon 192, these results need to be verified in further studies on a greater number of subjects.

Aged↗
PubMed2003

Myeloperoxidase polymorphisms in brain infarction. Association with infarct size and functional outcome.

Myeloperoxidase (MPO) has been shown to contribute to several diseases and more particularly to atherosclerosis through excessive ROS production via the MPO/H(2)O(2)/Cl(-) oxidation system. The aim of this study was to determine whether there is an association between MPO polymorphisms and brain infarction (BI), one of the main consequences of atherosclerosis. We investigated MPO G-463A and G-129A polymorphisms in 450 patients with BI confirmed by magnetic resonance imaging (MRI) and 450 controls of the GENIC (Génétique de l'Infarctus Cérébral) Study. Genotype determination of MPO was performed by polymerase chain reaction and allele-specific oligonucleotide hybridization (ASO). Genotype distributions for each of both MPO polymorphisms were found to be similar between cases and controls overall, and according to etiologic subtypes or gender. The frequency of the A allele of the G-463A polymorphism was 22% (95% confidence interval, 19.4 to 24.9) and the frequency of the A allele of the G-129A polymorphism was 6.8% (95% confidence interval, 5.3 to 8.6). The odds ratio (OR) for BI in carriers of the A allele of the G-129A polymorphism was 0.92 (95% confidence interval, 0.61 to 1.39), and the OR for BI in carriers of the A allele of the G-463A polymorphism was 1.15 (95% confidence interval, 0.88 to 1.52). No association between the main risk factors for BI such as hypertension, cholesterol, diabetes and MPO polymorphisms was found. In analyses restricted to cases, we identified an association between the A allele of the G-129A polymorphism and the size of the brain infarct (P=0.01). Furthermore, the A allele of the G-463A polymorphism was associated with a poorer functional short-term outcome as evaluated by the Rankin score (P=0.02). In conclusion, MPO polymorphisms were associated with the extent of brain damage and the functional outcome rather than with the risk of developing a BI.

Adolescent↗
PubMed2003

IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort.

There are no satisfactory data on circulating concentrations of inflammatory cytokines and their potential relationship with traditional and nontraditional atherosclerosis risk factors in a large healthy young population. The present study was conducted to examine, in 179 healthy families selected from the STANISLAS cohort, the association between interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), orosomucoid, haptoglobin, cell-adhesion molecules (ICAM-1, E-, L- and P-selectin) and lipid parameter concentrations. Age, BMI, white blood cells and tobacco consumption contributed to the variation of IL-6 concentrations. Age and tobacco contributed also to TNF-alpha variation. Taking into account potential covariates, we showed strong positive correlation between IL-6 and both inflammatory markers TNF-alpha and CRP in parents and in offspring (P<0.001). In parents, IL-6 was associated with ICAM-1 and L-selectin (P<0.01), while IL-6 and TNF-alpha predicted E-selectin in offspring only (0.001<P<0.01). Furthermore, IL-6 showed a strong negative relationship with apo A-1 and HDL-cholesterol in females only (P<0.001). This study demonstrated that in a large healthy family population, children included, levels of IL-6 are closely associated with traditional and non-traditional atherosclerosis risk factors. All these data are useful for defining the precise role of cytokines in atherosclerosis mechanisms in physiological conditions.

Adult↗
PubMed2003

Charge-based heterogeneity of human plasma lipoproteins at hypertriglyceridemia: capillary isotachophoresis study.

To reveal the metabolic links between and within pools of pro-atherogenic triglyceride(TG)-rich lipoproteins and anti-atherogenic high density lipoproteins (HDL), the changes in lipoprotein profile at hypertriglyceridemia were analyzed by capillary isotachophoresis. Plasma samples from patients with apoE3/3 phenotype were stained with a fluorescent probe NBD-C6-ceramide and lipoproteins resolved into six H-, one (V+I) and four L-components which belong to HDL, very low and intermediate density (VLDL+IDL) and low density lipoproteins (LDL), respectively. The expected correlation between the relative size of the combined fractions and lipid and apolipoprotein values was obtained confirming the validity of the approach. The new findings were obtained as follows. (1) The fast L-component correlated inversely with HDL-cholesterol (Chol), while intermediate and slow H-components correlated inversely with plasma and LDL-Chol and apoB. (2) The content of intermediate and slow H-components increased within H-pool and decreased relative TG-rich lipoproteins as hypertriglyceridemia rose due to the impairment of triglyceride hydrolysis by lipoprotein lipase within TG-rich particles. (3) A predictive value of the ratios of fast to slow H-components as an indicator of lecithin:cholesterol acyltransferase activity was demonstrated which tended to decrease at hypertriglyceridemia. (4) The L1/L2 ratio may be considered as an indicator of the accumulation of small dense LDL, which is a feature of clinically manifested atherogenic B-pattern. The competition between H(DL) and L(DL) particles for hepatic lipase and significant contribution of apoE to functional deficiency of H(DL) particles at hypertriglyceridemia are suggested.

Apolipoproteins E↗
PubMed2003

Association between Gly241Arg ICAM-1 gene polymorphism and serum sICAM-1 concentration in the Stanislas cohort.

Intracellular adhesion molecule-1 (ICAM-1), a cellular adhesion molecule that mediates the interaction of activated endothelial cells with leukocytes, is involved in various inflammatory and cardiovascular disorders. The relation between these markers and genetic polymorphism, however, remains to be elucidated. The aim of this study is to estimate the effect of a single-base polymorphism at codon 241 in exon 4 of ICAM-1 gene on serum sICAM-1 concentration in a healthy population, taking into account other biological determinants of sICAM-1 level. Serum sICAM-1 levels and the G/R241 polymorphism of the ICAM-1 gene were measured in a large healthy population consisting of 413 children aged 6-21 years and 363 adults aged 38-55 years extracted from the Stanislas cohort. The R241 allele was significantly associated with lower sICAM-1 levels and explained 3.4 and 1.9% of the sICAM-1 variability in children and adults, respectively. A codominant pattern contributed better to the model after adjustment for covariates as the RR homozygote effect was higher than that of the GR heterozygote. Moreover, significant independent associations were found between sICAM-1 and smoking, insulin resistance index (HOMA IR), interleukin-6 level, and alkaline phosphatase and aspartate aminotransferase activities. In conclusion, this study revealed a significant association between the G/R241 ICAM-1 polymorphism and serum sICAM-1 levels, probably due to the impairment in binding of ICAM-1 to leukocyte integrin Mac-1 protein.

Adolescent↗
PubMed2003

Changes in serum retinol, alpha-tocopherol, vitamin C, carotenoids, xinc and selenium after micronutrient supplementation during alcohol rehabilitation.

OBJECTIVE: To test the effect of a 21-day supplementation with moderate doses of antioxidant nutrients on biochemical indicators of vitamin, carotenoid and trace element levels in alcohol-dependent patients during a program of alcohol rehabilitation. DESIGN: A randomized double-blind trial was performed comparing two groups receiving daily either a combination of micronutrients (beta-carotene: 6 mg, vitamin C: 120 mg, vitamin E: 30 mg, zinc: 20 mg, selenium: 100 micro g) or a placebo. SUBJECTS: 106 alcohol-dependent patients 20 to 60 years of age without severe liver disease, hospitalized for a 21-day rehabilitation program. Measure of Outcome: Vitamin C, retinol, alpha-tocopherol, zeaxanthin/lutein, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, zinc and selenium were measured in serum, initially and after supplementation. RESULTS: (1) In the placebo group, after 21 days of rehabilitation, serum concentrations of vitamin C and all five carotenoids significantly increased, whereas retinol and alpha-tocopherol concentrations decreased; zinc and selenium levels were unaffected. (2) At the end of the hospital stay, serum indicators were significantly improved in the supplement group as compared to the placebo group for vitamin C, alpha-tocopherol, beta-carotene, zinc and selenium; conversely, lycopene changes were higher in the placebo group than in supplement group. (3) Of the serum antioxidants measured at entrance, only vitamin C was significantly depleted in heavy smokers, and, after the supplementation period, vitamin C was efficiently repleted in this later group. CONCLUSION: Our results indicate that a short-term supplementation with physiological doses of antioxidant vitamins, carotenoids and trace elements during alcohol rehabilitation clearly improves micronutrient status indicators. Heavy smokers in particular seem to respond to vitamin C supplementation.

Adult↗
PubMed2003

Family study of the relationship between height and cardiovascular risk factors in the STANISLAS cohort.

BACKGROUND: Short stature is a risk factor for coronary heart disease and is associated with an adverse cardiovascular profile. Mechanisms responsible for this association remain unknown. A genetic contribution to this association would imply a familial clustering between height and cardiovascular risk factors. METHODS: This study investigated whether lipids and blood pressure (BP) levels shared a common familial component with height. The sample included 865 nuclear families from the French STANISLAS cohort volunteering for a free health examination between 1993 and 1994. Within-individual correlations and familial intra-trait and cross-trait correlations were estimated using the Estimating Equation technique extended to a bivariate phenotype. RESULTS: Height negatively correlated to total and low density lipoprotein cholesterol (LDL-C) and triglycerides in both parents and offspring, and positively correlated to high density lipoprotein cholesterol (HDL-C) in parents only. In offspring, the correlation between height and HDL-C markedly increased with sexual maturation to reach after puberty the same value as in parents. The correlation of height with systolic BP was negative in fathers and positive in sons, whereas it was non-significant in mothers and daughters. The pattern of cross-trait familial correlations between height and LDL-C was compatible with the existence of a weak transmissible component explaining the relationship between these two traits. By contrast, the pattern observed for HDL-C and triglycerides was rather compatible with the influence of shared environmental factors. No familial clustering between height and BP levels was detected. CONCLUSIONS: The association between short stature and increased LDL-C might be partly of familial origin.

Adolescent↗
PubMed2003

Serum total antioxidant status, erythrocyte superoxide dismutase and whole-blood glutathione peroxidase activities in the Stanislas cohort: influencing factors and reference intervals.

The aim of this work was to describe the factors influencing the levels of three antioxidant markers -total antioxidant status, erythrocyte copper/zinc superoxide dismutase (SOD), whole-blood selenium glutathione peroxidase--and to establish their reference intervals in supposedly healthy subjects. The studied population included 463 subjects, i.e., 223 adults and 140 children aged 20 to 65 and 4 to 19 years, respectively. The effect of factors such as age, gender, body mass index, alcohol and tobacco consumption, menopause, drug intake, trace elements, transferrin, ferritin, albumin, bilirubin, haptoglobin, total proteins, uric acid, haemoglobin, and mean corpuscular volume of erythrocytes have been studied for the three antioxidant markers. Total antioxidant status (TAS) was higher in men than in women whatever the age (p < 0.001). Albumin and uric acid in men, women and girls, and total proteins in boys were significant determinants of TAS levels. Mean corpuscular volume of erythrocytes were negatively and significantly associated with SOD activity in men and in women (p < 0.01) but not in children. Among the studied determinants, none were found to influence the selenium glutathione peroxidase activity in the four groups. Reference intervals including the 90% confidence intervals were established by age and sex for the three antioxidant markers.

Adolescent↗
PubMed2003

PON1-192 phenotype and genotype assessments in 918 subjects of the Stanislas cohort study.

This study describes the factors of variation of the enzymes related to the PON1-192 phenotype assessment, i.e., basal paraoxonase, salt-stimulated paraoxonase and arylesterase activities, and compares the PON1-192 phenotype to the PON1-192 genotype assessments in supposedly healthy subjects issued from the Stanislas cohort study. The studied population included 918 subjects, i.e., 221 families including 441 adults and 477 children aged 4 to 58 years. Potential determinants such as age, gender, body mass index, alcohol and tobacco consumption, and oral contraceptive intake have been studied. The PON ratio (salt-stimulated paraoxonase/arylesterase) was trimodally distributed and the cut-off values used to differentiate the two homozygous (AA and BB phenotypes) from the heterozygous (AB phenotype) subjects were 3.0 and 7.0 in this study. In males, basal paraoxonase and salt-stimulated paraoxonase activities were not affected by alcohol consumption and current smoking, but basal paraoxonase activity was decreased by 15% by current smoking and was increased by 15% by oral contraceptive intake in females as was the salt-stimulated paraoxonase activity. The level of discordance between phenotype and genotype assessments was 7.2% (66/918). Most of the discrepancies were observed between the BB and AB phenotypes (4.25%).

Adolescent↗
PubMed2003

Pharmacogenomics of drugs affecting the cardiovascular system.

The variability in drug response originates partly from genetics, with possible consequences for drug efficacy, adverse effects, and toxicity. Until now, pharmacogenetics mainly indicated the best known source of variability, that is, the variability caused by drug metabolism. However, simultaneous progress in the knowledge of biochemical targets of drugs and of the human genome, together with the development of new technologies, revealed many new sources of human genetic variation, e.g., in receptors or transporters. Drugs are metabolized by various polymorphic phase I enzymes, including cytochromes P450 (CYP). Among them, the most relevant for the metabolism of cardiovascular drugs are CYP3A4, CYP2C9 or CYP2C19, and CYP2D6. The role of phase II enzymes is limited with regard to cardiovascular drugs biotransformation, but some polymorphisms (glutathion-S-transferase; GSH-T) are linked to cardiovascular risk. Phase III proteins or transporters, especially from the ABC family, must also be considered, as their polymorphisms affect cholesterol and other sterols transport. Among pharmacological targets, some proteins were identified as involved in interindividual variations in the response to cardiovascular drugs. Some examples are apolipoprotein E, angiotensin-converting enzyme, and the beta-adrenergic receptor. From the risk concept emphasizing impaired metabolism and adverse effects, we now moved to an approach, which is a personalized, genotype-dependent adaptation of therapy.

Cardiovascular Agents↗
PubMed2003

From transcriptomics to bibliomics.

BACKGROUND: Current biological investigations tend to operate with genomes, instead of genes as during the last century. It is possible to compare entire genomes, transcriptomes or proteomes, using alphanumeric data corresponding to the differential expression levels of thousands of genes. What remains difficult is to link array results to factual or bibliographical data and retrieve information that is highly structured and - in Shannon's sense - rare. MATERIAL/METHODS: We have developed a tool, Documentation and Information LIBrary (DILIB), that enables us to retrieve, organize and analyze huge amounts of data available on the Internet and related to microarray experiments. DILIB can link hundreds of differentially expressed genes - through their Single Identifier or GenBank accession number - to hundreds of Medline records, and can retrieve, analyze, and compare automatically thousands of non-trivial descriptors related to gene clusters. RESULTS: As exemplified with frequency comparison of MEdical Subject Headings and Registry Number descriptors, we reanalyzed the involvement of 'integrin', 'interleukin' and 'CD Antigens' in mesotheliomas. Thus, DILIB allowed us to: (i). associate literature to expressed genes, (ii). link functional transcriptomes in various experiments, (iii). associate specific descriptors to experiments, (iv). define new research areas, and eventually (v). find new functions for co-expressed genes. CONCLUSIONS: We propose a new concept, 'bibliomics', representing a subset of high quality and rare information, retrieved and organized by systematic literature-searching tools from existing databases, and related to a subset of genes functioning together in '-omic' sciences.

Databases, Genetic↗
PubMed2002

Biological and genetic determinants of serum apoC-III concentration: reference limits from the Stanislas Cohort.

Apolipoprotein C-III (apoC-III) is involved in triglycerides metabolism, and is therefore important for the pathogenesis of coronary heart diseases. However, to our knowledge serum apoC-III variation factors and reference limits have never been determined, so the aim of this study was to establish them and facilitate clinical usefulness. We measured serum apoC-III concentration of apparently healthy subjects of the Stanislas Cohort by an immunoturbidimetric method. Genetic polymorphisms within the APOC3, APOE, APOAIV, and LPL genes were determined by a multiplex PCR. Serum apoC-III concentration varied from 28.2 mg/l to 225.8 mg/l in the overall sample and between subjects variability was about 30%. Factors influencing apoC-III concentration were age, BMI in adult men, alcohol consumption in adults, oral contraceptive intake in women, the post-pubescent status in boys. The APOC3 1100T allele in adult men and the APOC3 -455C allele in boys were associated with increased apoC-III concentration. The APOA4 360His allele was associated with decreased apoC-III concentration in women. We also established reference limits of serum apoC-III concentration according to age and gender.

Adolescent↗
PubMed2002

Apolipoprotein E activates Akt pathway in neuro-2a in an isoform-specific manner.

Apolipoprotein E (apoE) is a ligand for members of the low density lipoprotein (LDL) receptor family, receptors highly expressed in neurons. A study of one of the mechanisms by which apoE might affect neuronal cell metabolism is reported herein. ApoE can induce Akt/protein kinase B phosphorylation in Neuro-2a via two different pathways. Both pathways are mediated by phosphatidylinositol 3-kinase and cAMP-dependent protein kinase. The first pathway is stimulated by apoE3 and E4, but not by E2, after a 1-h incubation. The process requires the binding of apoE to the heparan sulfate proteoglycan/LDL receptor-related protein complex. The second pathway is activated after a 2-h incubation of the cells, in another isoform-dependent manner (E2 = E3 dbl greater-than sign E4) and is mediated by calcium. Our results suggest that apoE might affect cell metabolism and survival in neurons in an isoform-specific manner by inducing novel signaling pathways.

Animals↗
PubMed2002

Extension of variance components approach to incorporate temporal trends and longitudinal pedigree data analysis.

Here we present a method that permits one to evaluate genetic effects and to detect genetic linkages by using serial observations of quantitative traits in pedigrees. We developed a statistical method that incorporates longitudinal family data and genetic marker information into an estimating equations framework. With this approach, we can study changes in components over time that measure polygenic and major genetic variances as well as shared and individual-specific environmental effects. Our method provides a measure of heritability from analysis of longitudinal data. Results using longitudinal family data from the Center for Preventive Medicine (Nancy, France) are presented. The results of our analysis show that the apolipoprotein E locus has no effect on interindividual variability in systolic blood pressure. We found that the longitudinal measure of heritability of systolic blood pressure is 0.32.

Apolipoproteins E↗
PubMed2002

Rapid spectrophotometric method for serum glutathione S-transferases activity.

BACKGROUND: Glutathione S-transferases (GST) are a family of polymorphic enzymes responsible for the metabolism of a broad range of xenobiotics including carcinogens and endogenous compounds. METHODS: The aim of this study was to develop a fully automated spectrophotometric method to determine serum GST activity. RESULTS: The method had a detection limit of 7 U/l. The within- and between-run repeatability reached 2% and 3%, respectively. The reproducibility tested over a 6-month period was 7%. Serum GST activity is stable for at least 1 week at +37, +4 and -20 degrees C, 1 month at -20 degrees C and 6 months at -80 and -196 degrees C. The GST activities were determined on 374 supposedly healthy subjects coming to the Center of Preventive Medicine for a health screening. The sample population comprised 178 males and 196 females 4-80 years of age. The mean value of the serum GST activity calculated for this healthy population was 28.2+/-3.0 U/l without gender difference (range from 20.0 to 38.0 U/l). The global interindividual variability reached 11%. CONCLUSIONS: This report describes a spectrophotometric assay for monitoring the serum GST activities in human. This method will be useful in examining the relationships between serum GST activities and the GST polymorphisms, especially pi-GST.

Acetaminophen↗