Document Detail


A common variant highly associated with plasma VEGFA levels also contributes to the variation of both LDL-C and HDL-C.
MedLine Citation:
PMID:  23204297     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vascular endothelial growth factor A (VEGFA) is among the most-significant stimulators of angiogenesis. Its effect on cardiovascular diseases and on the variation of related risk factors such as lipid parameters is considered important, although as yet unclear. Recently, we identified four common variants (rs6921438, rs4416670, rs6993770, and rs10738760) that explain up to 50% of the heritability of plasma VEGFA levels. In the present study, we aimed at assessing the contribution of these variants to the variation of blood lipid levels (including apoE, triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol levels (LDL-C and HDL-C)] in healthy subjects. The effect of these single-nucleotide polymorphisms (SNPs) on lipid levels was assessed using linear regression in discovery and replication samples (n = 1,006 and n = 1,145; respectively), followed by a meta-analysis. Their gene×gene and gene×environment interactions were also assessed. SNP rs6921438 was associated with HDL-C (β = -0.08 mmol/l, P(overall) = 1.2 × 10(-7)) and LDL-C (β = 0.13 mmol/l, P(overall) = 1.5 × 10(-4)). We also identified a significant association between the interaction rs4416670×hypertension and apoE variation (P(overall) = 1.7 × 10(-5)). Therefore, our present study shows a common genetic regulation between VEGFA and cholesterol homeostasis molecules. The SNP rs6921438 is in linkage disequilibrium with variants located in an enhancer- and promoter-associated histone mark region and could have a regulatory effect in the expression of surrounding genes, including VEGFA.
Authors:
Maria G Stathopoulou; Amélie Bonnefond; Ndeye Coumba Ndiaye; Mohsen Azimi-Nezhad; Said El Shamieh; Abdelsalam Saleh; Marc Rancier; Gerard Siest; John Lamont; Peter Fitzgerald; Sophie Visvikis-Siest
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-02
Journal Detail:
Title:  Journal of lipid research     Volume:  54     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-09     Completed Date:  2013-06-05     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  535-41     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Cholesterol, HDL / blood*
Cholesterol, LDL / blood*
Epistasis, Genetic / genetics
Female
Gene-Environment Interaction
Humans
Male
Polymorphism, Single Nucleotide*
Reproducibility of Results
Vascular Endothelial Growth Factor A / blood*,  genetics*
Chemical
Reg. No./Substance:
0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A
Comments/Corrections
Erratum In:
J Lipid Res. 2013 Mar;54(3):869

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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