| Evidence of how rs7575840 influences apolipoprotein B-containing lipid particles. | |
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MedLine Citation:
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PMID: 21393584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Recent genome-wide association studies identified a variant rs7575840 in the apolipoprotein B (APOB) gene region as associated with low-density lipoprotein (LDL) cholesterol. However, the underlying functional mechanism of this variant, which resides 6.5 kb upstream of APOB, has remained unknown. Our objective was to investigate rs7575840 for association with refined apoB-containing lipid particles, for replication in a Mexican population, and for its underlying functional mechanism. METHODS AND RESULTS: Our data show that rs7575840 is associated with serum apoB levels (P=4.85×10(-10)) and apoB-containing lipid particles, very small very-low-density lipoprotein, intermediate lipoprotein, and LDL particles (P=2×10(-5) to 9×10(-7)) in the Finnish Metabolic Syndrome in Men study sample (n=7710). Fine mapping of the APOB region using 43 single-nucleotide polymorphisms replicated the association of rs7575840 with apoB in a Mexican study sample (n=2666, P=3.33×10(-5)). Furthermore, our transcript analyses of adipose RNA samples from 175 subjects in the Finnish Metabolic Syndrome in Men study indicate that rs7575840 alters expression of APOB (P=1.13×10(-10)) and a regional noncoding RNA (BU630349) (P=7.86×10(-6)) in adipose tissue. CONCLUSIONS: It has been difficult to convert genome-wide association study associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB-containing lipid particles, as well as influencing expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant single-nucleotide polymorphism, rs7575840, may affect serum apoB, LDL cholesterol, and total cholesterol levels. |
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Authors:
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Blake E Haas; Daphna Weissglas-Volkov; Carlos A Aguilar-Salinas; Elina Nikkola; Laurent Vergnes; Ivette Cruz-Bautista; Laura Riba; Alena Stancakova; Johanna Kuusisto; Pasi Soininen; Antti J Kangas; Mika Ala-Korpela; Teresa Tusie-Luna; Markku Laakso; Päivi Pajukanta |
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Publication Detail:
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Type: Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-10 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 31 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-21 Completed Date: 2011-06-24 Revised Date: 2012-05-02 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1201-7 Citation Subset: IM |
Affiliation:
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Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, Gonda Center, Rm 6335B, 695 Charles E. Young Dr S, Los Angeles, CA 90095-7088, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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metabolism Aged Apolipoproteins B / blood, genetics* Biological Markers / blood Case-Control Studies Cholesterol, LDL / blood European Continental Ancestry Group / genetics Finland / epidemiology Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Humans Hypertriglyceridemia / blood, ethnology, genetics* Indians, North American / genetics Linear Models Lipoproteins, IDL / blood Lipoproteins, LDL / blood Lipoproteins, VLDL / blood Male Mexico / epidemiology Middle Aged Particle Size Pedigree Phenotype Polymorphism, Single Nucleotide* Risk Assessment Risk Factors Triglycerides / blood |
| Grant Support | |
ID/Acronym/Agency:
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HL-095056/HL/NHLBI NIH HHS; HL-28481/HL/NHLBI NIH HHS; P01 HL028481-23/HL/NHLBI NIH HHS; R01 HL095056-01/HL/NHLBI NIH HHS; R01 HL095056-02/HL/NHLBI NIH HHS; R01 HL095056-03/HL/NHLBI NIH HHS; R01 HL095056-04/HL/NHLBI NIH HHS; T32 HG002536-01/HG/NHGRI NIH HHS; T32 HG02536/HG/NHGRI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins B; 0/Biological Markers; 0/Cholesterol, LDL; 0/Lipoproteins, IDL; 0/Lipoproteins, LDL; 0/Lipoproteins, VLDL; 0/Triglycerides |
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