Abstract
PRIMARY dysbetalipoproteinaemia (broad-β disease, hyper-lipoproteinaemia type III) is a familial disorder of plasma lipoprotein metabolism associated with xanthomatosis and early onset of severe atherosclerotic vascular disease1–4. A defect in the catabolism of triglyceride-rich lipoproteins probably underlies the accumulation of atypical cholesterol-rich lipoproteins (very low density β lipoproteins, ‘β–VLDL’) in the Sf 12–400 density fraction5–7. The disorder is assumed to be rare8 and we have provided evidence for an autosomal recessive mode of inheritance9,10. Patients show a variant of one major protein component (Apo E) of VLDL1,12. Apo E is a glycoprotein of molecular weight ∼ 39,000 that splits into three main bands designated E-I (pI∼5.3), E-II (pI∼5.4) and E-III (pI∼5.55) in iso-electric focusing13. The Apo E variant is characterised by a deficiency of Apo E-III in triglyceride-rich lipoproteins. We report here that Apo E shows a genetic polymorphism determined by two alleles Apo En and Apo Ed. About 1% of the German population is homozygous for the allele Apo Ed and exhibits Apo E-III deficiency. All individuals of this genotype have a primary dysbetalipoproteinaemia but not necessarily hyperlipidaemia. This is therefore the most frequent monogenic dyslipoproteinaemia known in man.
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UTERMANN, G., HEES, M. & STEINMETZ, A. Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man. Nature 269, 604–607 (1977). https://doi.org/10.1038/269604a0
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DOI: https://doi.org/10.1038/269604a0
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