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. 1994 Sep;94(3):1252–1262. doi: 10.1172/JCI117443

Variable expression of familial dysbetalipoproteinemia in apolipoprotein E*2 (Lys146-->Gln) Allele carriers.

P de Knijff 1, A M van den Maagdenberg 1, D I Boomsma 1, A F Stalenhoef 1, A H Smelt 1, J J Kastelein 1, A D Marais 1, R R Frants 1, L M Havekes 1
PMCID: PMC295210  PMID: 8083367

Abstract

Genetic and biochemical studies were carried out in 96 relatives of six independently ascertained probands with familial dysbetalipoproteinemia (FD) carrying the APOE*2 (Lys146-->Gln) allele. Compared to noncarriers, the 40 heterozygous APOE*2 (Lys146-->Gln) allele carriers exhibited markedly increased mean levels of cholesterol and triglyceride in the very low density lipoproteins (VLDL) (1.89 +/- 0.37 vs 0.30 +/- 0.27 and 1.86 +/- 0.37 vs 0.68 +/- 0.27 mmol/liter, respectively) and plasma apolipoprotein (apo) E levels (28.1 +/- 1.6 vs 4.6 +/- 1.1 mg/dl), which is characteristic for FD. By means of a pedigree-based maximum likelihood method we calculated that carrier-status accounted for 57% and 71%, respectively, of the total variance of the ratio (VLDL + IDL)-cholesterol/plasma triglyceride and plasma apoE levels. APOE*2 (Lys146-->Gln) and APOE*3-Leiden allele carriers were found to differ significantly in: (a) plasma apoE levels, (b) in the amounts of triglycerides in the VLDL and VLDL + IDL fraction, and (c) in the amount of cholesterol in the VLDL and VLDL + IDL fraction relative to the amount of triglyceride in these fractions. In the APOE*2 (Lys146-->Gln) allele carriers the VLDL and VLDL + IDL fraction is relatively rich in triglycerides as compared with that in APOE*3-Leiden carriers. We hypothesize that these two rare mutations of apoE both lead to dominantly inherited forms of FD along different underlying metabolic defects.

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Selected References

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