Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease

Background: Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD).Methods: Four singl...

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Autores principales:	Xueyan Zhao, Jingjing Xu, Xiaofang Tang, Keyong Huang, Jiawen Li, Ru Liu, Lin Jiang, Yin Zhang, Dong Wang, Kai Sun, Bo Xu, Wei Zhao, Rutai Hui, Runlin Gao, Lei Song, Jinqing Yuan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	NPC1L1 HMGCR genetic variants SYNTAX score premature triple-vessel disease Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/27286a1d258b48fe84192bc0f05a96b1
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spelling	oai:doaj.org-article:27286a1d258b48fe84192bc0f05a96b12021-12-02T00:17:42ZEffect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease2297-055X10.3389/fcvm.2021.704501https://doaj.org/article/27286a1d258b48fe84192bc0f05a96b12021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.704501/fullhttps://doaj.org/toc/2297-055XBackground: Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD).Methods: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, and rs2073547) of NPC1L1; and three SNPs (rs12916, rs2303151, and rs4629571) of HMGCR were genotyped in 872 PTVD patients (males ≤ 50 years old and females ≤ 60 years old), and 401 healthy controls.Results: After adjusting for age and sex, rs12916 of HMGCR was associated with the risk of PTVD in dominance model [odds ratio (OR) = 1.68, 95% confidence intervals (CI): 1.29–2.18, P < 0.001], recessive model (OR = 1.43, 95% CI: 1.08–1.90, P = 0.013) and codominant model (OR = 1.38, 95% CI: 1.17–1.63, P < 0.001); meanwhile, rs4720470 of NPC1L1 was related to increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14–2.74, P = 0.013). Patients who carried both variant rs4720470 and rs12916 also had the risk of PTVD (P < 0.001); however, there were no correlation between these SNPs and the SNYTAX score (all P > 0.05).Conclusions: This is the first report that rs4720470 is a novel polymorphism of the NPC1L1 gene associated with PTVD, and rs12916 of HMGCR gene appears to be a strong genetic marker of PTVD. Our study may improve the early warning, therapeutic strategies and drug development of PTVD.Xueyan ZhaoJingjing XuXiaofang TangKeyong HuangJiawen LiRu LiuLin JiangYin ZhangDong WangKai SunBo XuWei ZhaoRutai HuiRunlin GaoLei SongJinqing YuanFrontiers Media S.A.articleNPC1L1HMGCRgenetic variantsSYNTAX scorepremature triple-vessel diseaseDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NPC1L1 HMGCR genetic variants SYNTAX score premature triple-vessel disease Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	NPC1L1 HMGCR genetic variants SYNTAX score premature triple-vessel disease Diseases of the circulatory (Cardiovascular) system RC666-701 Xueyan Zhao Jingjing Xu Xiaofang Tang Keyong Huang Jiawen Li Ru Liu Lin Jiang Yin Zhang Dong Wang Kai Sun Bo Xu Wei Zhao Rutai Hui Runlin Gao Lei Song Jinqing Yuan Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease
description	Background: Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD).Methods: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, and rs2073547) of NPC1L1; and three SNPs (rs12916, rs2303151, and rs4629571) of HMGCR were genotyped in 872 PTVD patients (males ≤ 50 years old and females ≤ 60 years old), and 401 healthy controls.Results: After adjusting for age and sex, rs12916 of HMGCR was associated with the risk of PTVD in dominance model [odds ratio (OR) = 1.68, 95% confidence intervals (CI): 1.29–2.18, P < 0.001], recessive model (OR = 1.43, 95% CI: 1.08–1.90, P = 0.013) and codominant model (OR = 1.38, 95% CI: 1.17–1.63, P < 0.001); meanwhile, rs4720470 of NPC1L1 was related to increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14–2.74, P = 0.013). Patients who carried both variant rs4720470 and rs12916 also had the risk of PTVD (P < 0.001); however, there were no correlation between these SNPs and the SNYTAX score (all P > 0.05).Conclusions: This is the first report that rs4720470 is a novel polymorphism of the NPC1L1 gene associated with PTVD, and rs12916 of HMGCR gene appears to be a strong genetic marker of PTVD. Our study may improve the early warning, therapeutic strategies and drug development of PTVD.
format	article
author	Xueyan Zhao Jingjing Xu Xiaofang Tang Keyong Huang Jiawen Li Ru Liu Lin Jiang Yin Zhang Dong Wang Kai Sun Bo Xu Wei Zhao Rutai Hui Runlin Gao Lei Song Jinqing Yuan
author_facet	Xueyan Zhao Jingjing Xu Xiaofang Tang Keyong Huang Jiawen Li Ru Liu Lin Jiang Yin Zhang Dong Wang Kai Sun Bo Xu Wei Zhao Rutai Hui Runlin Gao Lei Song Jinqing Yuan
author_sort	Xueyan Zhao
title	Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease
title_short	Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease
title_full	Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease
title_fullStr	Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease
title_full_unstemmed	Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease
title_sort	effect of npc1l1 and hmgcr genetic variants with premature triple-vessel coronary disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/27286a1d258b48fe84192bc0f05a96b1
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Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease

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