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Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels
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 K...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643101/ https://www.ncbi.nlm.nih.gov/pubmed/29036232 http://dx.doi.org/10.1371/journal.pone.0186446 |
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author | Lee, Chan Joo Lee, Yunbeom Park, Sungha Kang, Seok-Min Jang, Yangsoo Lee, Ji Hyun Lee, Sang-Hak |
author_facet | Lee, Chan Joo Lee, Yunbeom Park, Sungha Kang, Seok-Min Jang, Yangsoo Lee, Ji Hyun Lee, Sang-Hak |
author_sort | Lee, Chan Joo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5643101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56431012017-10-30 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 PLoS One Research Article 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. Public Library of Science 2017-10-16 /pmc/articles/PMC5643101/ /pubmed/29036232 http://dx.doi.org/10.1371/journal.pone.0186446 Text en © 2017 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lee, Chan Joo Lee, Yunbeom Park, Sungha Kang, Seok-Min Jang, Yangsoo Lee, Ji Hyun Lee, Sang-Hak Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels |
title | Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels |
title_full | Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels |
title_fullStr | Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels |
title_full_unstemmed | Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels |
title_short | Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels |
title_sort | rare and common variants of apob and pcsk9 in korean patients with extremely low low-density lipoprotein-cholesterol levels |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643101/ https://www.ncbi.nlm.nih.gov/pubmed/29036232 http://dx.doi.org/10.1371/journal.pone.0186446 |
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