Identification of mutations in the apolipoprotein B-100 gene and in the PCSK9 gene as the cause of hypocholesterolemia

Clinica Chimica Acta; International Journal of Clinical Chemistry
T P Leren, K E Berge

Abstract

Characterization of the normally occurring mutations as the cause of hypocholesterolemia may increase our understanding of the normal lipid metabolism. DNA from 93 unrelated hypocholesterolemic subjects with a mean (+/-SD) value for total serum cholesterol of 3.3 (+/-0.5) mmol/l) were subjected to DNA sequencing of the individual exons of the apolipoprotein B-100 (apoB-100) gene and of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene. The same analyses were also performed in 23 unrelated subjects with autosomal dominant hypercholesterolemia who had unusually low levels of total serum cholesterol. Of the 93 hypocholesterolemic subjects, 9 subjects (9.7%) were heterozygous for a truncating mutation in the apoB-100 gene and six subjects (6.5%) were heterozygous for a loss-of-function mutation in the PCSK9 gene. Of the 23 subjects with autosomal dominant hypercholesterolemia, four subjects (17.4%) were heterozygous for mutations in the apoB-100 gene. Truncating mutations in the apoB-100 gene are slightly more common as the cause of hypocholesterolemia compared to loss-of-function mutations in the PCSK9 gene. It appears that mutations in the apoB-100 gene may completely normalize the lipid profile in subjects with autosomal...Continue Reading

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Citations

Jan 18, 2011·Orphanet Journal of Rare Diseases·Amandine GeorgesMarie E Samson-Bouma
Nov 18, 2009·Clinica Chimica Acta; International Journal of Clinical Chemistry·Thea Bismo StrømTrond P Leren
Jul 9, 2016·Current Opinion in Lipidology·Kate HaralambosIan F W McDowell
Aug 20, 2008·Clinica Chimica Acta; International Journal of Clinical Chemistry·Trond P Leren, Knut Erik Berge

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