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

Amanda J. Hooper; A. David Marais; Donald M. Tanyanyiwa; John R. Burnett

doi:10.1016/j.atherosclerosis.2006.08.039

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

Amanda J. Hooper, A. David Marais, Donald M. Tanyanyiwa, John R. Burnett^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

321 Citations (Scopus)

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 ∼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.

Original language	English
Pages (from-to)	445-448
Number of pages	4
Journal	Atherosclerosis
Volume	193
Issue number	2
DOIs	https://doi.org/10.1016/j.atherosclerosis.2006.08.039
Publication status	Published - Aug 2007
Externally published	Yes

Keywords

Cholesterol
Mutation
Nonsense
PCSK9

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10.1016/j.atherosclerosis.2006.08.039

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@article{b63d629e2e1440eea7c01ddc49acfdb2,

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 ∼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.",

keywords = "Cholesterol, Mutation, Nonsense, PCSK9",

author = "Hooper, {Amanda J.} and Marais, {A. David} and Tanyanyiwa, {Donald M.} and Burnett, {John R.}",

note = "Funding Information: Thanks to Dr. George Mantiri and Ms. Joanna Brisbane for assisting with DNA extractions. This work was supported by grants from the Raine Medical Research Foundation, National Health & Medical Research Council (403908), and National Heart Foundation of Australia (G 139 1155). Thanks to the Lotterywest State Biomedical Genomics Facility, Clinical Department of Immunology and Biochemical Genetics, Royal Perth Hospital, for the use of the ABI 7900HT. Partial support was also obtained from the Medical Research Council of South Africa.",

year = "2007",

month = aug,

doi = "10.1016/j.atherosclerosis.2006.08.039",

language = "English",

volume = "193",

pages = "445--448",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

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T1 - The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population

AU - Hooper, Amanda J.

AU - Marais, A. David

AU - Tanyanyiwa, Donald M.

AU - Burnett, John R.

N1 - Funding Information: Thanks to Dr. George Mantiri and Ms. Joanna Brisbane for assisting with DNA extractions. This work was supported by grants from the Raine Medical Research Foundation, National Health & Medical Research Council (403908), and National Heart Foundation of Australia (G 139 1155). Thanks to the Lotterywest State Biomedical Genomics Facility, Clinical Department of Immunology and Biochemical Genetics, Royal Perth Hospital, for the use of the ABI 7900HT. Partial support was also obtained from the Medical Research Council of South Africa.

PY - 2007/8

Y1 - 2007/8

N2 - 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 ∼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.

AB - 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 ∼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.

KW - Cholesterol

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

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Keywords

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