Apolipoprotein E polymorphism in the Netherlands and its effect on plasma lipid and apolipoprotein levels

Abstract

By isoelectric focusing of delipidated sera followed by immunoblotting we studied the apolipoprotein (apo) E polymorphism in 2018 randomly selected 35-years-old males from three different areas in the Netherlands. Comparison of the APOE allele (E*2, E*3, and E*4) frequencies estimated in this study with those reported for several other population samples showed that there are marked differences between the Dutch population and the populations of Japan, New Zealand, Finland, and the United States. These differences in APOE allele frequencies appeared to be mainly due to differences in frequencies of the E*2 allele (decreased in Japan and Finland; increased in New Zealand) and the E*4 allele (increased in Finland; decreased in Japan and the United States). No difference in APOE allele frequencies was found between the Dutch population and the populations of West Germany and Scotland. Measurements of plasma cholesterol and apo B and E concentrations showed that the E*4 allele is associated with elevated plasma cholesterol and apo B levels and with decreased apo E concentrations, whereas the opposite is true for the E*2 allele. In the Dutch population, the sum of average allelic effects of the common APOE alleles on plasma cholesterol and apo B levels is 6.8% and 14.2%, respectively, of the total population mean. The total average allelic effect on plasma apo E concentrations was more pronounced (50.1%), suggesting that the APOE alleles primarily affect apo E concentrations rather than plasma cholesterol and apo B levels. This hypothesis is sustained by the observation that for plasma apo E levels the genetic variance associated with the APOE gene locus contributed about 18% to the total phenotypic variance. For plasma cholesterol and apo B this contribution was only 1.4% and 2.3% and is relatively low as compared with that reported for other population samples.

Elevated Remnant-Like Particles in Heterozygous Familial Hypercholesterolemia and Response to Statin Therapy

“…The apoE allele distribution was in Hardy-Weinberg equilibrium ( 2 ϭ3.59, PϾ0.1) in our FH sample, but the frequency of the ⑀-2 allele was lower than previously reported in the general Dutch population (0.047 and 0.082, respectively). 29 It is therefore unlikely that an overrepresentation of the ⑀-2 allele of the apoE gene contributed to our findings.…”

Should animal fats be back on the table? A critical review of the human health effects of animal fat

“…Each LDL-C particle has a single apoB molecule associated with it, and apoB expression is affected by insulin flux and the amount of lipid in the liver (Elam et al 1999;Veniant et al 1999), and so APOB gene expression and hence the number of LDL-C particles is partly driven by carbohydrate intake. It is also inversely related to the amount of apoE in circulation (Smit et al 1988;Utermann 1988), and although there is a major genetic effect on apoE expression due to variation at the apolipoprotein E (APOE) coding sequence, apoE expression is positively correlated with dietary cholesterol, oestrogen and SFA (Utermann et al 1979;Srivastava 1996;Srivastava et al 1996).…”

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

“…Ten unrelated carriers (two type III HLP patients and eight normolipidemic E2/2 subjects) were detected during a populationbased study among 2018 randomly selected 35-year-old men. 26 In total, 44 E2/2 subjects (9 type III HLP patients and 35 normolipidemic E2/2 subjects) were collected from the Rotterdam Study, a prospective cohort study of 6870 healthy persons aged 55 years and older, investigating determinants of chronic diseases. 27 In this study, we included 113 type III HLP patients and 52 normolipidemic E2/2 subjects.…”