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


RESULTS
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.


CONCLUSIONS
Our results show that the PCSK9 C679X variant has a marked cholesterol-lowering effect.
Hooper
Amanda J
AJ
Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia.
Marais
A David
AD
Tanyanyiwa
Donald M
DM
Burnett
John R
JR
D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood* / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000235:genetics*; D015030:Zimbabwe
D008078:Cholesterol, LDL; D018389:Codon, Nonsense; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases