Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke

Qi Gong,1,* Liping Ye,2,* Huiwen Gui,1 Jing Liu,1 Huanyin Li,1 Qian Sun1 1Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China; 2Nursing Department, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199,...

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Autores principales:	Gong Q, Ye L, Gui H, Liu J, Li H, Sun Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	ischemic stroke ANGPTL3 genetic atherosclerosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/d4b3754fc61a4cf09122350cb7d568db
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spelling	oai:doaj.org-article:d4b3754fc61a4cf09122350cb7d568db2021-12-02T05:42:34ZAssociation study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke1178-2021https://doaj.org/article/d4b3754fc61a4cf09122350cb7d568db2019-10-01T00:00:00Zhttps://www.dovepress.com/association-study-of-genetic-variants-of-the-angptl3-gene-and-suscepti-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Qi Gong,1,* Liping Ye,2,* Huiwen Gui,1 Jing Liu,1 Huanyin Li,1 Qian Sun1 1Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China; 2Nursing Department, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huanyin LiDepartment of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, 170 Shenlong Road, Minhang District, Shanghai 201199, People’s Republic of ChinaTel/Fax +86 216 492 3400Email li_huanyin@sina.comBackground: Stroke ranks as the third-leading cause of years of life lost worldwide. ANGPTL3 plays important roles in lipid metabolism, atherosclerosis, and occurrence of stroke. The purpose of this study was to evaluate associations of genetic variants in the ANGPTL3 gene with ischemic stroke (IS) risk.Methods: A case–control study was conducted to evaluate the associations of tag single-nucleotide polymorphisms (SNPs) of the ANGPTL3 gene and risk of IS, as well as serum lipid levels. Dual-luciferase reporter assays in the HEK293T cell line was conducted to evaluate the promoter activity of ANGPTL3 rs6690733.Results: We found rs6690733 (C vs A: OR 1.34, 95% CI 1.13–1.59; P=0.001) and rs12563308 (C vs T: OR 0.77, 95% CI 0.64–0.93, P=0.007) were significantly associated with susceptibility to IS. Even corrected for Bonferroni adjustment, the two variants were still significant (0.007×4=0.028). Carriers of the minor allele of SNP rs6690733 had significantly higher levels of TC and LDL-C, while carriers of the minor allele of SNP rs12563308 had significantly lower levels of TC and LDL-C (all P<0.05). For rs6690733, the luciferase assay showed that promoter activity was significantly increased by 67% of plasmids containing the minor C allele compared with the major A allele in HEK293 cells.Conclusion: Our study revealed genetic variants of the ANGPTL3 gene could contribute to susceptibility to IS through participating in the regulation of lipid metabolism.Keywords: ischemic stroke, ANGPTL3, genetic, atherosclerosisGong QYe LGui HLiu JLi HSun QDove Medical Pressarticleischemic strokeANGPTL3geneticatherosclerosisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 3015-3020 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischemic stroke ANGPTL3 genetic atherosclerosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	ischemic stroke ANGPTL3 genetic atherosclerosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Gong Q Ye L Gui H Liu J Li H Sun Q Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke
description	Qi Gong,1,* Liping Ye,2,* Huiwen Gui,1 Jing Liu,1 Huanyin Li,1 Qian Sun1 1Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China; 2Nursing Department, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huanyin LiDepartment of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, 170 Shenlong Road, Minhang District, Shanghai 201199, People’s Republic of ChinaTel/Fax +86 216 492 3400Email li_huanyin@sina.comBackground: Stroke ranks as the third-leading cause of years of life lost worldwide. ANGPTL3 plays important roles in lipid metabolism, atherosclerosis, and occurrence of stroke. The purpose of this study was to evaluate associations of genetic variants in the ANGPTL3 gene with ischemic stroke (IS) risk.Methods: A case–control study was conducted to evaluate the associations of tag single-nucleotide polymorphisms (SNPs) of the ANGPTL3 gene and risk of IS, as well as serum lipid levels. Dual-luciferase reporter assays in the HEK293T cell line was conducted to evaluate the promoter activity of ANGPTL3 rs6690733.Results: We found rs6690733 (C vs A: OR 1.34, 95% CI 1.13–1.59; P=0.001) and rs12563308 (C vs T: OR 0.77, 95% CI 0.64–0.93, P=0.007) were significantly associated with susceptibility to IS. Even corrected for Bonferroni adjustment, the two variants were still significant (0.007×4=0.028). Carriers of the minor allele of SNP rs6690733 had significantly higher levels of TC and LDL-C, while carriers of the minor allele of SNP rs12563308 had significantly lower levels of TC and LDL-C (all P<0.05). For rs6690733, the luciferase assay showed that promoter activity was significantly increased by 67% of plasmids containing the minor C allele compared with the major A allele in HEK293 cells.Conclusion: Our study revealed genetic variants of the ANGPTL3 gene could contribute to susceptibility to IS through participating in the regulation of lipid metabolism.Keywords: ischemic stroke, ANGPTL3, genetic, atherosclerosis
format	article
author	Gong Q Ye L Gui H Liu J Li H Sun Q
author_facet	Gong Q Ye L Gui H Liu J Li H Sun Q
author_sort	Gong Q
title	Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke
title_short	Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke
title_full	Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke
title_fullStr	Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke
title_full_unstemmed	Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke
title_sort	association study of genetic variants of the angptl3 gene and susceptibility to ischemic stroke
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/d4b3754fc61a4cf09122350cb7d568db
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_version_	1718400260065198080

Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke

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