title: The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population.
abstract: 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.
authors.affiliation: Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.forename: A David
authors.initials: AD
authors.lastname: Marais
authors.forename: Donald M
authors.initials: DM
authors.lastname: Tanyanyiwa
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
mesh_terms: 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
chemical_list: D008078:Cholesterol, LDL; D018389:Codon, Nonsense; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases