Trond P Leren1, Knut Erik Berge. 1. Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, NO 0027 Oslo, Norway. trond.leren@rikshospitalet.no
Abstract
BACKGROUND: Characterization of the normally occurring mutations as the cause of hypocholesterolemia may increase our understanding of the normal lipid metabolism. METHODS: 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. RESULTS: 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. CONCLUSION: 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 dominant hypercholesterolemia, whereas loss-of-function mutations in the PCSK9 gene do not have a sufficient cholesterol-lowering capacity.
BACKGROUND: Characterization of the normally occurring mutations as the cause of hypocholesterolemia may increase our understanding of the normal lipid metabolism. METHODS: 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. RESULTS: 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. CONCLUSION: 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 dominant hypercholesterolemia, whereas loss-of-function mutations in the PCSK9 gene do not have a sufficient cholesterol-lowering capacity.
Authors: Michael Winther; Shoshi Shpitzen; Or Yaacov; Jakob Landau; Limor Oren; Linda Foroozan-Rosenberg; Naama Lev Cohain; Daniel Schurr; Vardiela Meiner; Auryan Szalat; Shai Carmi; Michael R Hayden; Eran Leitersdorf; Ronen Durst Journal: J Lipid Res Date: 2019-08-06 Impact factor: 5.922
Authors: Amandine Georges; Jessica Bonneau; Dominique Bonnefont-Rousselot; Jacqueline Champigneulle; Jean P Rabès; Marianne Abifadel; Thomas Aparicio; Jean C Guenedet; Eric Bruckert; Catherine Boileau; Alain Morali; Mathilde Varret; Lawrence P Aggerbeck; Marie E Samson-Bouma Journal: Orphanet J Rare Dis Date: 2011-01-14 Impact factor: 4.123