R. Gueguen

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.

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.

DNA polymorphisms of human apolipoprotein A‐IV gene: frequency and effects on lipid, lipoprotein and apolipoprotein levels in a French population

Genetic polymorphisms of apolipoprotein (apo) A‐IV have been shown to influence lipoprotein metabolism in some human populations. In this study, we have evaluated the physiological effect of three apo A‐IV polymorphisms (Gln360‐ < His, Thr347‐ < Ser and XbaI within the second intron of the apo A‐IV gene), in a French population, on seven quantitative traits: total cholesterol and triglycerides, cholesterol of HDL, apo A‐IV, apo B, apo A‐I and glucose. The polymorphism at amino‐acid 360 was determined by direct analysis of polymerase chain reaction products. The allele frequencies were 0.92 for the A‐IV1 and 0.08 for the A‐IV2 allele. The genetic polymorphism at codon 347 was investigated by allele‐specific oligonucleotide hybridization. The allele frequencies of the two alleles, A‐IV347Thr and A‐IV347Ser, were 0.78 and 0.22, respectively. The XbaI polymorphism was investigated by polymerase chain reaction followed by XbaI restriction enzyme digestion of the amplified products. The frequencies of the two apo A‐IV alleles, XbaI‐1 and XbaI‐2, were 0.79 and 0.21, respectively. None of the three apo A‐IV polymorphisms had a significant effect on lipoprotein, apolipoprotein and glucose levels.

Apolipoprotein E genotype ε4/ε2 in the STANISLAS Cohort Study - Dominance of the ε2 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 (ε4/ε2, ε2/ε2 or ε4/ε4) is scarce. Our work was designed to answer the following questions: 1. Are the allelic effects of ε2 and ε4 on lipid traits additive or dominant? 2. If there is additivity, do the allelic effects of ε2 and ε4 have the same magnitude? 3. Are the allelic effects neutralised in ε4/ε2 individuals who are under the influence of both rare alleles?

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.

Frequency and effects of the apolipoprotein A‐IV polymorphism

Plasma from 158 presumed healthy nuclear families has been analyzed by high‐resolution, two‐dimensional electrophoresis to study the frequency and effects of the genetic polymorphism in human apolipoprotein A‐IV. Two common alleles, apo A‐IV 1 and apo A‐IV 2 were detected with relative frequencies of 0.943 and 0.057, respectively. Autosomal codominant transmission of these two alleles coded for by a single structural locus was demonstrated. Furthermore, we studied the effects of this apo A‐IV variability on total plasma cholesterol, triglyceride, glucose levels and gamma‐glutamyltransferase activity. Statistically significant differences among apo A‐IV genotypes for the average glucose level were detected. The average effect of the apo A‐IV 1 allele was to lower plasma glucose levels by 0.013 mmol/l, whereas the average effect of the apo A‐IV 2 allele was to raise glucose levels by 0.213 mmol/l.

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.