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.

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.

Family study of lipoprotein lipase gene polymorphisms and plasma triglyceride levels.

To better characterize the role of the lipoprotein lipase (LPL) gene in the determination of triglyceride levels in healthy subjects, a study was performed in 193 nuclear families (384 parents, means age = 42.0 +/- 5.2 years; 399 offspring, mean age = 14.6 +/- 4.3 years) volunteering to have a free health checkup examination. The pattern of familial resemblance was compatible with a zero correlation between spouses, a weak father-offspring correlation (0.099 +/- 0.054; P < 0.07), and significant mother-offspring (0.235 +/- 0.053; P < 10(-4)) and sib-sib (0.294 +/- 0.064; P < 10(-4)) correlations. Associations of triglyceride levels with the LPL HindIII and PvuII polymorphisms were investigated by a familial measured genotype analysis, specifying sex- and age-dependent polymorphism effects. The effects associated with both polymorphisms were significant only in fathers, the H+ and P+ alleles being associated with raised triglyceride levels. The HindIII and PvuII polymorphisms explained 3.5% and 3%, respectively, of the variability of triglycerides in fathers. The relationship was weakened after prior adjustment on body mass index, but remained significant for PvuII. Because of the lack of effect in mothers and offspring, the polymorphisms did not contribute to the covariance of triglyceride levels in relatives. In conclusion, this family study showed a weak relationship of the HindIII and PvuII polymorphisms to plasma triglyceride levels in young healthy male subjects. The effects detectable only in fathers suggest a possible modulation of the LPL expression by hormonal or lifestyle factors.

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 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 < 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 < 0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

Apolipoprotein E genotype epsilon 4/epsilon 2 in the STANISLAS Cohort Study--dominance of the epsilon 2 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 (epsilon 4/epsilon 2, epsilon 2/epsilon 2 or epsilon 4/epsilon 4) is scarce. Our work was designed to answer the following questions: 1. Are the allelic effects of epsilon 2 and epsilon 4 on lipid traits additive or dominant? 2. If there is additivity, do the allelic effects of epsilon 2 and epsilon 4 have the same magnitude? 3. Are the allelic effects neutralised in epsilon 4/ epsilon 2 individuals who are under the influence of both rare alleles? Allelic effects on apoB and apoE serum levels were codominant. Allelic models are thus not adequate to study the influence of apoE polymorphism on these traits. Allelic effects were additive for total cholesterol, LDL-C, HDL-C and apoAI, with epsilon 2 having a greater impact than epsilon 4. Serum levels differed significantly between epsilon 4/epsilon 2 and epsilon 3/epsilon 3 individuals only for apoE (p < 0.001) and for apoB (p < 0.05).

Apolipoprotein E: an important gene and protein to follow in laboratory medicine.

The human apolipoprotein (apo) E gene is polymorphic, with three common alleles (epsilon 2, epsilon 3, epsilon 4) coding for three isoforms (E2, E3, E4). The isoforms differ from each other by a single amino acid substitution, and also differ in their binding affinity for the four apo E receptors. Apo E polymorphism is an important determinant of risk for the development of cardiovascular and Alzheimer diseases, the prevalence of the epsilon 4 allele being increased in both kinds of patients compared with control subjects. Furthermore, the prevalence of the epsilon 4 allele differs among populations (range 5-40%, respectively, for Taiwanese and Papua New Guineans). Genotyping or phenotyping needs to be introduced in clinical laboratories. The choice of the method should be based on the types of patients who are examined. The apo E genotype is also a determinant of apo E plasma concentration. Standardization of apo E measurement is an important prerequisite before investigating the clinical interest of plasma apo E concentration. Determination of apo E genotype/phenotype and later the plasma concentration are expected to yield useful clinical laboratory information.