Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels

Chan Joo Lee, Yunbeom Lee, Sungha Park, Seok Min Kang, Yangsoo Jang, Ji Hyun Lee, Sang Hak Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Screening of variants, related to lipid metabolism in patients with extreme cholesterol levels, is a tool used to identify targets affecting cardiovascular outcomes. The aim of this study was to examine the prevalence and characteristics of rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol (LDL-C) levels. Methods: Among 13,545 participants enrolled in a cardiovascular genome cohort, 22 subjects, whose LDL-C levels without lipid-lowering agents were 1 percentile (48 mg/dL) of Korean population, were analyzed. Two target genes, APOB and PCSK9, were sequenced by targeted next-generation sequencing. Prediction of functional effects was conducted using SIFT, PolyPhen-2, and Mutation Taster, and matched against a public database of variants. Results: Eight rare variants of the two candidate genes (five in APOB and three in PCSK9) were found in nine subjects. Two subjects had more than two different rare variants of either gene (one subject in APOB and another subject in APOB/PCSK9). Conversely, 12 common variants (nine in APOB and three in PCSK9) were discovered in 21 subjects. Among all variants, six in APOB and three in PCSK9 were novel. Several variants previously reported functional, including c.C277T (p.R93C) and c.G2009A (p.G670E) of PCSK9, were found in our population. Conclusions: Rare variants of APOB or PCSK9 were identified in nine of the 22 study patients with extremely low LDL-C levels, whereas most of them had common variants of the two genes. The common novelty of variants suggested polymorphism of the two genes among them. Our results provide rare genetic information associated with this lipid phenotype in East Asian people.

Original languageEnglish
Article numbere0186446
JournalPloS one
Volume12
Issue number10
DOIs
Publication statusPublished - 2017 Oct

Fingerprint

low density lipoprotein cholesterol
LDL Cholesterol
Genes
genes
antilipemic agents
Lipids
Lipid Metabolism
lipid metabolism
Population
Polymorphism
Cholesterol
cholesterol
genetic polymorphism
Genome
Databases
Screening
screening
Phenotype
mutation
phenotype

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

@article{cbfcdf0035ea4cefabbcd621a7efcdfa,
title = "Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels",
abstract = "Background: Screening of variants, related to lipid metabolism in patients with extreme cholesterol levels, is a tool used to identify targets affecting cardiovascular outcomes. The aim of this study was to examine the prevalence and characteristics of rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol (LDL-C) levels. Methods: Among 13,545 participants enrolled in a cardiovascular genome cohort, 22 subjects, whose LDL-C levels without lipid-lowering agents were 1 percentile (48 mg/dL) of Korean population, were analyzed. Two target genes, APOB and PCSK9, were sequenced by targeted next-generation sequencing. Prediction of functional effects was conducted using SIFT, PolyPhen-2, and Mutation Taster, and matched against a public database of variants. Results: Eight rare variants of the two candidate genes (five in APOB and three in PCSK9) were found in nine subjects. Two subjects had more than two different rare variants of either gene (one subject in APOB and another subject in APOB/PCSK9). Conversely, 12 common variants (nine in APOB and three in PCSK9) were discovered in 21 subjects. Among all variants, six in APOB and three in PCSK9 were novel. Several variants previously reported functional, including c.C277T (p.R93C) and c.G2009A (p.G670E) of PCSK9, were found in our population. Conclusions: Rare variants of APOB or PCSK9 were identified in nine of the 22 study patients with extremely low LDL-C levels, whereas most of them had common variants of the two genes. The common novelty of variants suggested polymorphism of the two genes among them. Our results provide rare genetic information associated with this lipid phenotype in East Asian people.",
author = "Lee, {Chan Joo} and Yunbeom Lee and Sungha Park and Kang, {Seok Min} and Yangsoo Jang and Lee, {Ji Hyun} and Lee, {Sang Hak}",
year = "2017",
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language = "English",
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Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels. / Lee, Chan Joo; Lee, Yunbeom; Park, Sungha; Kang, Seok Min; Jang, Yangsoo; Lee, Ji Hyun; Lee, Sang Hak.

In: PloS one, Vol. 12, No. 10, e0186446, 10.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels

AU - Lee, Chan Joo

AU - Lee, Yunbeom

AU - Park, Sungha

AU - Kang, Seok Min

AU - Jang, Yangsoo

AU - Lee, Ji Hyun

AU - Lee, Sang Hak

PY - 2017/10

Y1 - 2017/10

N2 - Background: Screening of variants, related to lipid metabolism in patients with extreme cholesterol levels, is a tool used to identify targets affecting cardiovascular outcomes. The aim of this study was to examine the prevalence and characteristics of rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol (LDL-C) levels. Methods: Among 13,545 participants enrolled in a cardiovascular genome cohort, 22 subjects, whose LDL-C levels without lipid-lowering agents were 1 percentile (48 mg/dL) of Korean population, were analyzed. Two target genes, APOB and PCSK9, were sequenced by targeted next-generation sequencing. Prediction of functional effects was conducted using SIFT, PolyPhen-2, and Mutation Taster, and matched against a public database of variants. Results: Eight rare variants of the two candidate genes (five in APOB and three in PCSK9) were found in nine subjects. Two subjects had more than two different rare variants of either gene (one subject in APOB and another subject in APOB/PCSK9). Conversely, 12 common variants (nine in APOB and three in PCSK9) were discovered in 21 subjects. Among all variants, six in APOB and three in PCSK9 were novel. Several variants previously reported functional, including c.C277T (p.R93C) and c.G2009A (p.G670E) of PCSK9, were found in our population. Conclusions: Rare variants of APOB or PCSK9 were identified in nine of the 22 study patients with extremely low LDL-C levels, whereas most of them had common variants of the two genes. The common novelty of variants suggested polymorphism of the two genes among them. Our results provide rare genetic information associated with this lipid phenotype in East Asian people.

AB - Background: Screening of variants, related to lipid metabolism in patients with extreme cholesterol levels, is a tool used to identify targets affecting cardiovascular outcomes. The aim of this study was to examine the prevalence and characteristics of rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol (LDL-C) levels. Methods: Among 13,545 participants enrolled in a cardiovascular genome cohort, 22 subjects, whose LDL-C levels without lipid-lowering agents were 1 percentile (48 mg/dL) of Korean population, were analyzed. Two target genes, APOB and PCSK9, were sequenced by targeted next-generation sequencing. Prediction of functional effects was conducted using SIFT, PolyPhen-2, and Mutation Taster, and matched against a public database of variants. Results: Eight rare variants of the two candidate genes (five in APOB and three in PCSK9) were found in nine subjects. Two subjects had more than two different rare variants of either gene (one subject in APOB and another subject in APOB/PCSK9). Conversely, 12 common variants (nine in APOB and three in PCSK9) were discovered in 21 subjects. Among all variants, six in APOB and three in PCSK9 were novel. Several variants previously reported functional, including c.C277T (p.R93C) and c.G2009A (p.G670E) of PCSK9, were found in our population. Conclusions: Rare variants of APOB or PCSK9 were identified in nine of the 22 study patients with extremely low LDL-C levels, whereas most of them had common variants of the two genes. The common novelty of variants suggested polymorphism of the two genes among them. Our results provide rare genetic information associated with this lipid phenotype in East Asian people.

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