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Identification of genes affecting apolipoprotein B secretion following siRNA-mediated gene knockdown in primary human hepatocytes

Highlights ► siRNA-mediated gene knockdown in primary human hepatocytes was used to identify potential causal genes affecting lipid traits. ► Approximately 100 GWAS loci significantly affecting human plasma lipid levels were identified. ► A total of 191 genes from 74 loci were selected and subjected...

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Published in:Atherosclerosis 2012-05, Vol.222 (1), p.154-157
Main Authors: Shen, Xun, Wang, Wei, Wang, Liangsu, Houde, Caroline, Wu, Weizhen, Tudor, Matt, Thompson, John R, Sisk, Christine McCrary, Hubbard, Brian, Li, Jing
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cited_by cdi_FETCH-LOGICAL-c498t-827b848edea444795761fc725926f91472e74773961f39a2b6cab5dec91b3cfa3
cites cdi_FETCH-LOGICAL-c498t-827b848edea444795761fc725926f91472e74773961f39a2b6cab5dec91b3cfa3
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container_start_page 154
container_title Atherosclerosis
container_volume 222
creator Shen, Xun
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Sisk, Christine McCrary
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description Highlights ► siRNA-mediated gene knockdown in primary human hepatocytes was used to identify potential causal genes affecting lipid traits. ► Approximately 100 GWAS loci significantly affecting human plasma lipid levels were identified. ► A total of 191 genes from 74 loci were selected and subjected to siRNA-mediated gene knockdown. ► Four genes (PARP10, HP, FUT1, and LPAR2) were identified and verified as affecting ApoB secretion.
doi_str_mv 10.1016/j.atherosclerosis.2012.02.012
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Vascular system ; Cardiovascular ; Cholesterol ; Cholesterol, HDL - blood ; Cholesterol, LDL - blood ; Fucosyltransferases - genetics ; Galactoside 2-alpha-L-fucosyltransferase ; Gene Knockdown Techniques ; genes ; Genome-Wide Association Study ; Haptoglobins - genetics ; hepatocytes ; Hepatocytes - metabolism ; high density lipoprotein cholesterol ; Humans ; Lipids ; loci ; low density lipoprotein cholesterol ; Medical sciences ; Poly(ADP-ribose) Polymerases - genetics ; Proprotein Convertase 9 ; Proprotein Convertases - metabolism ; Proto-Oncogene Proteins - genetics ; Receptors, Lysophosphatidic Acid - genetics ; RNA, Small Interfering - pharmacology ; secretion ; Serine Endopeptidases - metabolism ; siRNA ; small interfering RNA ; subtilisin ; Surgery (general aspects). Transplantations, organ and tissue grafts. 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Vascular system</subject><subject>Cardiovascular</subject><subject>Cholesterol</subject><subject>Cholesterol, HDL - blood</subject><subject>Cholesterol, LDL - blood</subject><subject>Fucosyltransferases - genetics</subject><subject>Galactoside 2-alpha-L-fucosyltransferase</subject><subject>Gene Knockdown Techniques</subject><subject>genes</subject><subject>Genome-Wide Association Study</subject><subject>Haptoglobins - genetics</subject><subject>hepatocytes</subject><subject>Hepatocytes - metabolism</subject><subject>high density lipoprotein cholesterol</subject><subject>Humans</subject><subject>Lipids</subject><subject>loci</subject><subject>low density lipoprotein cholesterol</subject><subject>Medical sciences</subject><subject>Poly(ADP-ribose) Polymerases - genetics</subject><subject>Proprotein Convertase 9</subject><subject>Proprotein Convertases - metabolism</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Receptors, Lysophosphatidic Acid - genetics</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>secretion</subject><subject>Serine Endopeptidases - metabolism</subject><subject>siRNA</subject><subject>small interfering RNA</subject><subject>subtilisin</subject><subject>Surgery (general aspects). 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Vascular system</topic><topic>Cardiovascular</topic><topic>Cholesterol</topic><topic>Cholesterol, HDL - blood</topic><topic>Cholesterol, LDL - blood</topic><topic>Fucosyltransferases - genetics</topic><topic>Galactoside 2-alpha-L-fucosyltransferase</topic><topic>Gene Knockdown Techniques</topic><topic>genes</topic><topic>Genome-Wide Association Study</topic><topic>Haptoglobins - genetics</topic><topic>hepatocytes</topic><topic>Hepatocytes - metabolism</topic><topic>high density lipoprotein cholesterol</topic><topic>Humans</topic><topic>Lipids</topic><topic>loci</topic><topic>low density lipoprotein cholesterol</topic><topic>Medical sciences</topic><topic>Poly(ADP-ribose) Polymerases - genetics</topic><topic>Proprotein Convertase 9</topic><topic>Proprotein Convertases - metabolism</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Receptors, Lysophosphatidic Acid - genetics</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>secretion</topic><topic>Serine Endopeptidases - metabolism</topic><topic>siRNA</topic><topic>small interfering RNA</topic><topic>subtilisin</topic><topic>Surgery (general aspects). 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subjects Apolipoprotein A-I - metabolism
Apolipoprotein B
Apolipoproteins B - metabolism
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
blood lipids
Cardiology. Vascular system
Cardiovascular
Cholesterol
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Fucosyltransferases - genetics
Galactoside 2-alpha-L-fucosyltransferase
Gene Knockdown Techniques
genes
Genome-Wide Association Study
Haptoglobins - genetics
hepatocytes
Hepatocytes - metabolism
high density lipoprotein cholesterol
Humans
Lipids
loci
low density lipoprotein cholesterol
Medical sciences
Poly(ADP-ribose) Polymerases - genetics
Proprotein Convertase 9
Proprotein Convertases - metabolism
Proto-Oncogene Proteins - genetics
Receptors, Lysophosphatidic Acid - genetics
RNA, Small Interfering - pharmacology
secretion
Serine Endopeptidases - metabolism
siRNA
small interfering RNA
subtilisin
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the heart
triacylglycerols
Triglycerides - blood
title Identification of genes affecting apolipoprotein B secretion following siRNA-mediated gene knockdown in primary human hepatocytes
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