Variation in the vascular endothelial growth factor gene, carotid intima-media thickness and the risk of acute myocardial infarction.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor, but its role in atherogenesis is still unclear. Our goal was to study whether three variants of the VEGF gene, previously associated with VEGF production, are linked to atherosclerosis defined as carotid intima-media thickness (IMT) and as the risk of acute myocardial infarction (AMI).


METHODS
Three VEGF gene single nucleotide polymorphisms (SNPs) (-2578A>C rs699947, -634C>G rs2010963 and +936C>T rs3025039) were genotyped in 516 control subjects of the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort and in 251 survivors of AMI. In the OPERA cohort, the genotyped SNPs were analysed for their association with IMT. The SNPs were also analysed for their association with the risk of AMI, a complication of advanced atherosclerosis. In addition, haplotype frequencies and their associated effects on IMT and on the risk of AMI were estimated.


RESULTS
None of the single genotyped polymorphisms was significantly associated with overall IMT or with the risk of AMI. However, the haplotype CCC was associated with higher overall IMT without plaques in women (p = 0.01, haplotypic effect +0.03 mm), the haplotype CCT with higher IMT without plaques in the internal carotid artery in men (p = 0.001, +0.11), while the haplotype AGT was associated with reduced AMI risk (p = 0.015, OR = 0.46).


CONCLUSIONS
Variation in the VEGF gene is weakly associated with IMT and the risk of AMI, but the effect can only be observed when the information of the SNPs is combined by constructing haplotypes.
Kangas-Kontio
Tiia
T
Institute of Clinical Medicine, Department of Internal Medicine, Oulu University Hospital and Biocenter Oulu, Finland.
Tapanainen
Jari M
JM
Huikuri
Heikki
H
Savolainen
Eeva-Riitta
ER
Päivänsalo
Markku
M
Kauma
Heikki
H
Kesäniemi
Y Antero
YA
Savolainen
Markku J
MJ
Kakko
Sakari
S
D000328:Adult; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A