title: Ethnic differences in the frequency of the cardioprotective C679X PCSK9 mutation in a West African population.
abstract: PCSK9 is a liver-secreted blood protein that promotes the degradation of low-density lipoprotein receptors, leading to reduced hepatic uptake of plasma cholesterol. Nucleotide variations in its gene have been linked to hypo- and hyper-cholesterolemia. Two nonsense mutations, Y142X and C679X, are associated to lifelong hypocholesterolemia and a remarkable protection against coronary heart disease (CHD) in African Americans. The aim of this study was to determine the frequency of these cardioprotective mutations in West Africans. Subjects (n = 520) from different ethnic groups were recruited in Burkina-Faso, Benin, and Togo. Only the C679X mutation was detected. All carriers were heterozygous. The overall heterozygosity frequency was 3.3%. It varied significantly among ethnic groups, ranging from 0% to 6.9%. The overall high frequency of the cardioprotective C679X mutation in Africa may contribute to the lower incidence of CHD on this continent. The interethnic frequency differences may reflect historical settlement and migration patterns in the region, possibly combined with positive selection for the mutation driven by yet-unknown environmental factors.
authors.affiliation: Chronic Disease Program, Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Canada.
authors.forename: Francine
authors.initials: F
authors.lastname: Sirois
authors.forename: Elias
authors.initials: E
authors.lastname: Gbeha
authors.forename: Ambaliou
authors.initials: A
authors.lastname: Sanni
authors.forename: Michel
authors.initials: M
authors.lastname: Chretien
authors.forename: Damian
authors.initials: D
authors.lastname: Labuda
authors.forename: Majambu
authors.initials: M
authors.lastname: Mbikay
mesh_terms: D001541:Benin / Q000208:ethnology; D044383:Black People / Q000235:genetics*; D002050:Burkina Faso / Q000208:ethnology; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D018389:Codon, Nonsense; D003327:Coronary Disease / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D011153:Population / Q000235:genetics*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000235:genetics*; D014037:Togo / Q000208:ethnology; D001741:Black or African American
chemical_list: D008078:Cholesterol, LDL; D018389:Codon, Nonsense; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases