Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Identification of a Functional Apolipoprotein E Promoter Polymorphism Regulating Plasma Apolipoprotein E Concentration

Identification of a Functional Apolipoprotein E Promoter Polymorphism Regulating Plasma... Identification of a Functional Apolipoprotein E Promoter Polymorphism Regulating Plasma Apolipoprotein E Concentration Maria Nastase Mannila, Hovsep Mahdessian, Anders Franco-Cereceda, Gösta Eggertsen, Ulf de Faire, Ann-Christine Syvänen, Per Eriksson, Anders Hamsten, Ferdinand M. van ’t Hooft Objective—There is compelling evidence that the plasma apolipoprotein E (APOE) concentration, in addition to the APOE ε2/ε3/ε4 genotype, influences plasma lipoprotein levels, but the functional genetic variants influencing the plasma APOE concentration have not been identified. Approach and Results—Genome-wide association studies in 2 cohorts of healthy, middle-aged subjects identified the APOE locus as the only genetic locus showing robust associations with the plasma APOE concentration. Fine-mapping of the APOE locus confirmed that the rs7412 ε2-allele is the primary genetic variant responsible for the relationship with plasma APOE concentration. Further mapping of the APOE locus uncovered that rs769446 (−427T/C) in the APOE promoter is independently associated with the plasma APOE concentration. Expression studies in 199 human liver samples demonstrated that the rs769446 C-allele is associated with increased APOE mRNA levels (P=0.015). Transient transfection studies and electrophoretic mobility shift assays in human hepatoma HepG2 cells corroborated the role of rs769446 in transcriptional regulation of APOE. However, no relationships were found between rs769446 genotype and plasma http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Identification of a Functional Apolipoprotein E Promoter Polymorphism Regulating Plasma Apolipoprotein E Concentration

Loading next page...
 
/lp/wolters-kluwer-health/identification-of-a-functional-apolipoprotein-e-promoter-polymorphism-ASneiIlAML

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Copyright
© 2013 American Heart Association, Inc.
ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/ATVBAHA.112.300353
pmid
23430611
Publisher site
See Article on Publisher Site

Abstract

Identification of a Functional Apolipoprotein E Promoter Polymorphism Regulating Plasma Apolipoprotein E Concentration Maria Nastase Mannila, Hovsep Mahdessian, Anders Franco-Cereceda, Gösta Eggertsen, Ulf de Faire, Ann-Christine Syvänen, Per Eriksson, Anders Hamsten, Ferdinand M. van ’t Hooft Objective—There is compelling evidence that the plasma apolipoprotein E (APOE) concentration, in addition to the APOE ε2/ε3/ε4 genotype, influences plasma lipoprotein levels, but the functional genetic variants influencing the plasma APOE concentration have not been identified. Approach and Results—Genome-wide association studies in 2 cohorts of healthy, middle-aged subjects identified the APOE locus as the only genetic locus showing robust associations with the plasma APOE concentration. Fine-mapping of the APOE locus confirmed that the rs7412 ε2-allele is the primary genetic variant responsible for the relationship with plasma APOE concentration. Further mapping of the APOE locus uncovered that rs769446 (−427T/C) in the APOE promoter is independently associated with the plasma APOE concentration. Expression studies in 199 human liver samples demonstrated that the rs769446 C-allele is associated with increased APOE mRNA levels (P=0.015). Transient transfection studies and electrophoretic mobility shift assays in human hepatoma HepG2 cells corroborated the role of rs769446 in transcriptional regulation of APOE. However, no relationships were found between rs769446 genotype and plasma

Journal

Arteriosclerosis, Thrombosis, and Vascular BiologyWolters Kluwer Health

Published: May 1, 2013

There are no references for this article.