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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: Long-term follow-up and treatment response
Arteriosclerosis, Thrombosis, and Vascular Biology, Volume 25, No. 12, Year 2005
Notification
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Description
Objective - Analysis of long-term (30 years) clinical history and response to treatment of 13 patients with the D374Y mutation of PCSK9 (PCSK9 patients) from 4 unrelated white British families compared with 36 white British patients with heterozygous familial hypercholesterolemia attributable to 3 specific mutations in the low-density lipoprotein (LDL) receptor gene (LDLR) known to cause severe phenotype. Methods and Results - The PCSK9 patients, when compared with the LDLR patients, were younger at presentation (20.8±14.7 versus 30.2±15.7 years; P=0.003), had higher pretreatment serum cholesterol levels (13.6±2.9 versus 9.6±1.6 mmol/L; P=0.004) that remained higher during treatment with simvastatin (10.1±3.0 versus 6.5±0.9 mmol/L; P=0.006), atorvastatin (9.6±2.9 versus 6.4±1.0 mmol/L; P=0.006), or current lipid-lowering therapy, including LDL apheresis and partial ileal bypass in 2 PCSK9 patients (7.0±1.6 versus 5.4±1.0 mmol/L; P=0.001), and were affected >10 years earlier by premature coronary artery disease (35.2±4.8 versus 46.8±8.9 years; P=0.002). LDL from PCSK9 patients competed significantly less well for binding to fibroblast LDL receptors than LDL from either controls or LDLR patients. Conclusions - These British PCSK9 patients with the D374Y mutation have an unpredictably severe clinical phenotype, which may be a unique feature for this cohort, and requires early and aggressive lipid-lowering management to prevent cardiovascular complications. © 2005 American Heart Association, Inc.
Authors & Co-Authors
Naoumova, Rossitza P.
United Kingdom, London
Hammersmith Hospital
Tosi, Isabella
United Kingdom, London
Hammersmith Hospital
Patel, Dilip
United Kingdom, London
Hammersmith Hospital
Neuwirth, Clare
United Kingdom, London
Hammersmith Hospital
Horswell, Stuart
United Kingdom, London
Hammersmith Hospital
Marais, Adrian David
South Africa, Cape Town
University of Cape Town
van Heyningen, Charles
United Kingdom, Liverpool
University Hospital
Soutar, Anne Katherine
United Kingdom, London
Hammersmith Hospital
Statistics
Citations: 186
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1161/01.ATV.0000190668.94752.ab
ISSN:
10795642
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health
Noncommunicable Diseases
Study Design
Cohort Study