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| Status |
Public on Sep 01, 2011 |
| Title |
Evidence of mechanism how rs7575840 influences apolipoprotein B containing lipid particles |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Objective: Recent genome-wide association studies (GWAS) identified a variant rs7575840 in the apolipoprotein B (APOB) gene region to be associated with LDL-C. However, the underlying functional mechanism of this variant that 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 non-Caucasian Mexican population; and for underlying functional mechanism. Methods and Results Our data show that rs7575840 is associated with serum apoB levels (P=4.85x10-10) and apoB containing lipid particles, very small VLDL, IDL and LDL particles (P=2x10-5 - 9x10-7) in the Finnish METSIM study sample (n=7,710). Fine mapping of the APOB region using 43 SNPs replicated the association of rs7575840 with apoB in a Mexican study sample (n=2,666, P=3.33x10-05). Furthermore, our transcript analyses of adipose RNA samples from 175 Finnish METSIM subjects indicate that rs7575840 alters expression of APOB (P=1.13x10-10) and a regional non-coding RNA (BU630349) (P=7.86x10-6) in adipose tissue. Conclusions It has been difficult to convert GWAS associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB containing lipid particles as well as influences expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant SNP rs7575840 may affect serum apoB, LDL-C, and TC levels.
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| Overall design |
175 samples, no replicates
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| Contributor(s) |
Haas BE, Weissglas-Volkov D, Aguilar-Salinas CA, Nikkola E, Vergnes L, Cruz-Bautista I, Riba L, Stancakova A, Kuusisto J, Soininen P, Kangas AJ, Ala-Korpela M, Tusie-Luna T, Laakso M, Pajukanta P |
| Citation(s) |
21393584 |
| Submission date |
Mar 03, 2011 |
| Last update date |
Aug 16, 2018 |
| Contact name |
Blake Edwin Haas |
| Organization name |
UCLA
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| Lab |
Gonda Center, Room 6335
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| Street address |
695 Charles E. Young Drive South
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
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| Samples (175)
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| Relations |
| BioProject |
PRJNA138477 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27666_RAW.tar |
6.2 Mb |
(http)(custom) |
TAR |
| GSE27666_non-normalized.txt.gz |
52.1 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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