The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population

• Published in: Atherosclerosis Vol. 193; no. 2; pp. 445 - 448
• Main Authors: Hooper, Amanda J., Marais, A. David, Tanyanyiwa, Donald M., Burnett, John R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.08.2007; Elsevier
• Subjects: Adult; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Brain; Cardiology. Vascular system; Cardiovascular; Cholesterol; Cholesterol, LDL - blood; Cholesterol, LDL - genetics; Codon, Nonsense; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Genetic Predisposition to Disease; Genotype; Humans; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - genetics; Investigative techniques of hemodynamics; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mutation; Nonsense; PCSK9; Proprotein Convertase 9; Proprotein Convertases; Serine Endopeptidases - genetics; Zimbabwe; PCSK9; Nonsense; Mutation; Cholesterol; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Vascular disease; Lipoprotein LDL; Missense mutation; Atherosclerosis; Dyslipemia; Human; Serine endopeptidases; Enzyme; Negroid; Metabolic diseases; Cholesterol LDL; Genotype; Subtilisin; Genetic disease; Peptidases; Hypercholesterolemia; Kexin; Hydrolases; Comparative study; African American
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2006.08.039

Missense mutations in the proprotein convertase subtilisin/kexin type 9 gene ( PCSK9) can cause familial hypercholesterolemia. However, two nonsense variants of PCSK9, Y142X and C679X, found in ∼2% of black American subjects, are associated with a 28% reduction in mean low density lipoprotein (LDL)–cholesterol. We sought to determine the frequency and effect of these nonsense variants in an African population. PCSK9 genotypes were determined in 653 black African women attending two antenatal clinics in Zimbabwe. C679X occurred in 3.7% of subjects and was associated with a 27% reduction in LDL–cholesterol (1.6 ± 0.3 mmol/L versus 2.2 ± 0.7 mmol/L in non-carriers). We did not observe the Y142X variant. Our results show that the PCSK9 C679X variant has a marked cholesterol-lowering effect.