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

• 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
• Format: Article
• Language: English
• 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
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2012.02.012

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.