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. METHODS AND 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.
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. METHODS AND 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 PCSK9C679X variant has a marked cholesterol-lowering effect.
Authors: Zhengdong D Zhang; Sofiya Milman; Jhih-Rong Lin; Shayne Wierbowski; Haiyuan Yu; Nir Barzilai; Vera Gorbunova; Warren C Ladiges; Laura J Niedernhofer; Yousin Suh; Paul D Robbins; Jan Vijg Journal: Nat Metab Date: 2020-07-27
Authors: Bomie Han; Patrick I Eacho; Michael D Knierman; Jason S Troutt; Robert J Konrad; Xiaohong Yu; Krista M Schroeder Journal: J Lipid Res Date: 2014-04-28 Impact factor: 5.922
Authors: Kevin Fitzgerald; Maria Frank-Kamenetsky; Svetlana Shulga-Morskaya; Abigail Liebow; Brian R Bettencourt; Jessica E Sutherland; Renta M Hutabarat; Valerie A Clausen; Verena Karsten; Jeffrey Cehelsky; Saraswathy V Nochur; Victor Kotelianski; Jay Horton; Timothy Mant; Joseph Chiesa; James Ritter; Malathy Munisamy; Akshay K Vaishnaw; Jared A Gollob; Amy Simon Journal: Lancet Date: 2013-10-03 Impact factor: 79.321
Authors: Joyce C Y Chan; Derek E Piper; Qiong Cao; Dongming Liu; Chadwick King; Wei Wang; Jie Tang; Qiang Liu; Jared Higbee; Zhen Xia; Yongmei Di; Susan Shetterly; Ziva Arimura; Heather Salomonis; William G Romanow; Stephen T Thibault; Richard Zhang; Ping Cao; Xiao-Ping Yang; Timothy Yu; Mei Lu; Marc W Retter; Gayle Kwon; Kirk Henne; Oscar Pan; Mei-Mei Tsai; Bryna Fuchslocher; Evelyn Yang; Lei Zhou; Ki Jeong Lee; Mark Daris; Jackie Sheng; Yan Wang; Wenyan D Shen; Wen-Chen Yeh; Maurice Emery; Nigel P C Walker; Bei Shan; Margrit Schwarz; Simon M Jackson Journal: Proc Natl Acad Sci U S A Date: 2009-05-14 Impact factor: 11.205