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Biomedical subjects

Bernard Herbeth

Publications and source records attributed to Bernard Herbeth.

9 recordsLinked to original sources

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↗

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↗

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↗

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↗

An isocratic liquid chromatographic method with diode-array detection for the simultaneous determination of alpha-tocopherol, retinol, and five carotenoids in human serum.

An isocratic high-performance liquid chromatography (HPLC) method for the simultaneous determination of alpha-tocopherol, retinol, and five carotenoids (lutein-zeaxanthin, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene) in human serum is described. Serum samples are deproteinized with ethanol and extracted once with n-hexane. Resulting extracts are injected onto a C18 reversed-phase column eluted with methanol-acetonitrile-tetrahydrofuran (75:20:5, v/v/v), and full elution of all the analytes is realized isocratically within 20 min. The detection is operated using three channels of a diode-array spectrophotometer at 290, 325, and 450 nm for tocopherol, retinol, and the carotenoids, respectively. An internal standard is used for each channel, which improves precision. The choice of internal standards is discussed, as well as the extraction protocol and the need for adding an antioxidant during the extraction and chromatographic steps. The analytical recoveries for liposoluble vitamins and carotenoids are more than 85%. Intra-assay relative standard deviation (RSD) values (n = 20) for measured concentrations in serum range from 3.3% (retinol) to 9.5% (lycopene), and interassay RSDs (n = 5) range from 3.8% (alpha-tocopherol) to 13.7% (beta-cryptoxanthin). The present method is used to quantitate the cited vitamins in healthy subjects (n = 168) from ages 9 to 55 years old.

Adolescent↗

Apolipoprotein E in apolipoprotein B (apo B)- and non-apo B-containing lipoproteins in 3523 participants in the Stanislas cohort: biological variation and genotype-specific reference limits.

BACKGROUND: Apolipoprotein (apo) E is a component of two major classes of plasma lipoproteins, apo B- (apo E-LpB) and non-apo B-containing (apo E-Lp-non-B) lipoproteins. The factors that affect total apo E in particles [lipoprotein E (LpE), apo E-Lp-non-B, and apo E-LpB], are incompletely characterized. METHODS: We studied the determinants of these lipoparticles in a sample population of presumably healthy individuals: 1784 children (age range, 8-18 years) and 1739 adults (age range, 19-50 years). Serum concentrations of LpE and apo E-Lp-non-B were measured by electroimmunoassays, and the concentration of apo E-LpB was calculated by a difference method. RESULTS: Serum LpE and apo E-Lp-non-B were higher in females than in males. Their concentrations decreased with age until 20-25 years and then increased in men but not in women. apo E-LpB concentrations increased up to 20-25 years and were similar in both sexes. Thereafter, adult men had higher values than women. Individuals carrying the epsilon2 allele had higher mean apo E-Lp-non-B concentrations and lower apo E-LpB concentrations than did individuals carrying the epsilon3 allele. Individuals with the epsilon4 allele showed an inverse profile compared with those with the epsilon2 allele. Age, gender, the common apo E polymorphism, puberty, serum lipid concentrations, and alcohol consumption were significantly associated with total LpE, apo E-Lp-non-B, and apo E-LpB concentrations. Reference limits were established according to age, gender, and the common apo E polymorphism. CONCLUSIONS: Because measurements of LpE, apo E-Lp-non-B, and apo E-LpB concentrations may improve cardiovascular risk assessment, the proposed reference limits will aid interpretation of the results in clinical or therapeutic trials.

Adolescent↗

Changes in serum apolipoprotein and lipoprotein profile after alcohol withdrawal: effect of apolipoprotein E polymorphism.

BACKGROUND: Apolipoprotein (Apo) E genotype and alcohol consumption or withdrawal strongly affect lipoprotein (Lp) metabolism and, as with any genetic and environmental factors, they might interact. The aim of this study was to investigate this gene/environment interaction by analyzing the effect of the apoE genotype on the alcohol withdrawal-induced alterations in the serum Apo and Lp profile. METHODS: ApoE genotypes and concentrations of serum cholesterol, triglyceride, and Lps containing apoA-I, A-II, B, E, and C-III were determined in 84 male alcohol abusers before and after 3 weeks of abstinence. RESULTS: After withdrawal, concentrations of serum apoA-I, LpA-I, LpA-I/A-II, apoC-III, LpC-III-non-B, apoE, and LpE-non-B significantly decreased, whereas those of triglycerides and apoB increased; levels of cholesterol, LpC-III:B, and LpB:E were not affected. ANOVA shows that apoE polymorphism effects were quite similar before and after alcohol withdrawal on all serum Apos and Lps (the interaction term between withdrawal and apoE genotype was not significant). The only interaction term that was borderline significant (p < or = 0.10) concerned the apoB concentration. Before withdrawal, no association between apoB level and apoE polymorphism was observed, whereas after abstinence, a borderline significant (p < or = 0.10) gradient of concentration across the three groups of subjects (epsilon2 carriers < epsilon3/epsilon3 < epsilon4 carriers) was noticed. CONCLUSIONS: Alcohol abstinence causes major changes in the antiatherogenic Apos and Lps and may increase those known to be atherogenic. Heavy alcohol consumption seems to alter the effect of apoE polymorphism on apoB levels, and further investigations are needed to clarify the mechanisms involved in this phenomenon: a defect in sialylation of apoE, formation of acetaldehyde adducts on apoB, or both.

Adult↗