Josiane Steinmetz

Prevalence of Hepatitis B and Hepatitis C Virus Infections in France in 2004: Social Factors Are Important Predictors After Adjusting for Known Risk Factors

To monitor the prevalence of hepatitis B and hepatitis C a cross‐sectional survey was conducted in 2004 among French metropolitan residents. A complex sampling design was used to enroll 14,416 adult participants aged 18–80 years. Data collected included demographic and social characteristics and risk factors. Sera were tested for anti‐HCV, HCV‐RNA, anti‐HBc and HBsAg. Data were analyzed with SUDAAN® software to provide weighted estimates for the French metropolitan resident population. The overall anti‐HCV prevalence was 0.84% (95% CI: 0.65–1.10). Among anti‐HCV positive individuals, 57.4% (95% CI: 43.2–70.5) knew their status. Factors associated independently with positive anti‐HCV were drug use (intravenous and nasal), blood transfusion before 1992, a history of tattoos, low socioeconomic status, being born in a country where anti‐HCV prevalence >2.5%, and age >29 years. The overall anti‐HBc prevalence was 7.3% (95%: 6.5–8.2). Independent risk factors for anti‐HBc were intravenous drug use, being a man who has sex with men, low socioeconomic status, a stay in a psychiatric facility or facility for the mentally disabled, <12 years of education, being born in a country where HBsAg prevalence >2%, age >29 and male sex. The HCV RNA and HBsAg prevalence were 0.53% (95% CI: 0.40–0.70) and 0.65% (95% CI: 0.45–0.93), respectively. Among HBsAg positive individuals, 44.8% (95% CI: 22.8–69.1) knew their status. Anti‐HCV prevalence was close to the 1990s estimates whereas HBsAg prevalence estimate was greater than expected. Screening of hepatitis B and C should be strengthened and should account for social vulnerability. J. Med. Virol. 82:546–555, 2010.

Objectives, Design and Recruitment of a Familial and Longitudinal Cohort for Studying Gene-Environment Interactions in the Field of Cardiovascular Risk: The Stanislas Cohort

Abstract 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) 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. 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 °C) has been established.

Plasma lecithin: cholesterol acyltransferase ― reference values and effects of xenobiotics

Plasma lecithin:cholesterol acyltransferase (LCAT) has been measured by an enzymatic method. We did not observe any significant sex variations, but age variations were found. In females, LCAT activities are stable up to 40 years (60 mumol . 1.1 . h-1 at the 50th centile). Also, from 50 years the median increased progressively to 76 mumol . 1-1 . h-1. In males, the activity increased from 52 to 71 mumol . 1-1 . h-1 at the 50th centile in two age groups (15-20 years and 50 years). The effect of some xenobiotics on LCAT activity was studied. We observed an increase in activity of 33% in males when the daily alcoholic beverage consumption ranged from 0 to more than 0.5 litre of wine or beer. LCAT activity increased in children who were treated with hypolipidemic drugs (fenofibrate, Lipanthyl). In boys, the mean enzyme activity increased to 35% (p less than 0.05). The increase was greater in girls (75%, p less than 0.01). Treatment with anticonvulsant drugs gave a decrease in LCAT activity of 32-46%.

High Sensitivity C-Reactive Protein: Biological Variations and Reference Limits

Abstract Serum C-reactive protein (CRP) concentration was determined for 3605 subjects using an immunonephelometric assay improved to provide greater sensitivity. Subjects were from 5 to 75 years old and belonging to 1003 nuclear families recruited from the Stanislas Coh o rt Study between January 1994 and August 1995. Sample values for CRP ranged from 0.17 mg/l to 100 mg/l. Geometric means (mean − SD; mean + SD) were in the 5–14 years old group 0.37 (0.17–1.07) mg/l, in the 15–28 years old group 0.47 (0.17–1.38) mg/l and in the 29–75 years old group 0.98 (0.34–2.85) mg/l. For women, the geometric means were 0.38 (0.17–1.10) mg/l, 0.62 (0.20–1.90) mg/l and 0.98 mg/l (0.31–3.13) mg/l respectively. The interindividual variability ranged from 138% to 759% among different age classes. Biological factors associated with CRP concentration variations were examined and accounted for 25% of the CRP variability in men and 40% in women. The main biological factors statistically associated with CRP concentration variations in men were: drugs, leukocyte count, body mass index, tobacco consumption, age, and in women: drugs, leukocyte count, age, body mass index and hemoglobin concentration. These factors were used to define the exclusion and partition criteria when obtaining the reference samples. Medians for reference values ranged from 0.20 to 0.68 mg/l in males and from 0.20 to 0.78 mg/l in women.

Multivariate genetic analysis of high density lipoprotein particles.

The aim of this study was to investigate the effect of genetic factors on three components of plasma high density lipoproteins, HDL-cholesterol (HDL-C), apolipoprotein A-I (apo A-I) and lipoprotein particle Lp A-I (Lp A-I), which contains apo A-I but not apo A-II. These analyses were carried out on 106 nuclear families with one or more children (407 subjects) who volunteered for health screening at the Center for Preventive Medicine, Vandoeuvre, France. After adjustment by stepwise multiple linear regression analysis for age, gender, weight, height, ponderosity, alcohol consumption, smoking habits, and hormonal treatment in females, a multifactorial model (considering the effect of polygenes, individual, specific, environmental and common household factors) was fitted to each variable separately. The hypothesis of no common household effects was accepted for each of the traits. The contribution of genetic factors to inter-individual variance was larger than the contribution of environmental factors for apo A-I (h2 = 0.81) and Lp A-I (h2 = 0.63) but not for HDL-C (h2 = 0.44). Bivariate analyses were carried out by parameterizing covariance components between traits. The genetic correlations were always significantly different from zero. They were estimated to be 0.73 between HDL-C and apo A-I, 0.40 between HDL-C and Lp A-I, 0.51 between apo A-I and Lp A-I. These results suggest that HDL-C, apo A-I and Lp A-I are only in part affected by the same genes and that the measurement of lipids as well as the apo A-I and Lp A-I gives complementary and different information on the metabolic and genetic aspects.

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 polymorphisms, the apo E polymorphism and two polymorphisms 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 PvulII/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 e4 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.

Biological variations in hyperlipidemic children and adolescents treated with fenofibrate

Beside their pharmacological action drugs may have unexpected side effects which must be known and taken into account in the interpretation of laboratory tests. In this work, we followed 17 hyperlipidemic subjects, aged 4-19 years, treated with fenofibrate only. We performed several plasma tests before and during treatment. The hypolipidemic action of fenofibrate was evident: decreases of cholesterol and triglycerides mean values were, respectively, 22% and 39% after 3 months of treatment. Other plasma constituents were also significantly decreased: uric acid, 20%; bilirubin, 19%; alkaline phosphatases, 15%. The aminotransferase activities (both AST and ALT) were increased in only four subjects after 3 months. The highest values were 88 U/l for AST and 109 U/l for ALT (the initial values were, respectively, 28 U/l and 23 U/l). These activities decreased when the treatment was stopped. These variations were isolated and transient.

Reference Limits of Apolipoprotein A-I and Apolipoprotein B Using an IFCC Standardized Immunonephelometric Method

An important collaborative study organized by the IFCC enabled the selection of international reference materials and the standardization of commercially available methods by the use of common calibrators. In this paper, we report the reference limits of apolipoprotein A-I and apolipoprotein B in a selected healthy French population. The apolipoprotein measurements were performed on BNA Behring using reagents and protocols supplied by the manufacturer: the standard sera were calibrated using the IFCC-WHO reference preparations (SP1 and SP3). In addition, the apolipoprotein B protocol was modified by the addition of a supplementary reagent to reduce the interference by lipaemic samples on immunonephelometric measurement. In a sample of 115 random serum samples, there was a decrease in mean concentration between non-standardized and standardized methods: -4.8% for apolipoprotein A-I and -4.7% for apolipoprotein B. The reference limits for apolipoprotein A-I are unaffected by gender between 4 and 14 years, thereafter vary with age and gender until 40 years and with gender alone between 40 and 60 years. For apolipoprotein B, the variation with gender is only significant between 30 and 49 years.

Soluble transferrin receptor (sTfR): biological variations and reference limits.

Abstract The aim of this study was to establish soluble serum transferrin receptor (sTfR) reference limits. sTfR was measured in 885 healthy subjects from 3 to 91 years old (433 men, 409 women), without hematological abnormalities, using an immunonephelometric assay. The sTfR median concentrations in our population decreased gradually from the group aged 3–10 years to the group aged 21–40 years, then there were no changes in the older groups except for the females >60 years of age. The interindividual variability ranged from 12.6% to 30.3% among different age groups, and the analytical variability was 5%. Biological factors and other factors associated with sTfR concentration variation were examined and accounted for 35% of the sTfR variability in men aged 20 years or less, and 18% in those older than 20 years. Also, they accounted for 45% of the variability in women aged 20 years or less and 14% in those older than 20 years. The main factors statistically associated with sTfR concentration in males were ferritin, orosomucoid, hemoglobin, and tobacco in all age groups and only mean corpuscular volume (MCV) in males less than 20 years old. In the females the main factors were age, orosomucoid, and hemoglobin in all age groups, MCV and tobacco in females less than 20 years old, and ferritin and physical activity in females more than 20 years old. These factors were used to define the exclusion and partition criteria for obtaining the reference samples. Medians for reference values were: 1.60 mg/l in the 3–10-year old group (males and females); 1.42 mg/l in males between 11 and 20 years of age, and 1.33 mg/l in females of the same age. In the other age groups, the median of the reference values was 1.16 mg/l, except in females over 60 years old, for whom it was 1.26 mg/l.

Apo B signal peptide insertion/deletion polymorphism is involved in postprandial lipoparticles' responses

The changes in postprandial concentrations of five lipoparticles (LpC-III, LpC-III:B, LpC-IIInoB, LpA-I and LpA-I:A-II) were studied on 144 apparently healthy (71 male and 73 female) subjects during the 4 h following the ingestion of a 1.260 kJ milkshake. The influence of apo B signal peptide polymorphisms, apo E polymorphism, and other factors including age, gender, BMI, tobacco and alcohol consumption on the postprandial responses of lipoparticles was investigated. Apo-A-I-containing lipoparticles were not influenced during the 4 h following the test meal except for LpA-I:A-II, which decreased in women. LpA-I:A-II is the only particle that showed a gender-dependent change in postprandial concentration. Apo-CIII-containing lipoparticles showed significant postprandial variations. Particles containing both apo B and apo C-III (total LpC-III and LpC-III:B), mainly present in VLDL fraction, had significantly different postprandial responses among the genotypes of the apo B signal peptide polymorphism. Homozygotes for Del allele showed a decrease of LpC-III:B concentrations over the 4 h, whereas Ins/Ins homozygotes and Ins/Del heterozygotes had a peak in concentration at 2 h. The apo B signal peptide polymorphism explained 2.3% of the variance of LpCIII:B, whereas apo E polymorphism did not influence the postprandial concentrations of any lipoparticles.