A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels.
BACKGROUND
Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Strong interindividual variations of VEGF plasma levels have been reported previously. Aim of the present study was to search for mutations in the 3' untranslated region (3'-UTR) of the VEGF gene and to analyze their relation to VEGF plasma levels.


METHODS
The complete 3'-UTR (nucleotide 700-2622) of the VEGF gene was screened for sequence variations by single-strand conformation polymorphism (SSCP) analysis. Frequencies of mutated alleles were determined in 119 healthy subjects; VEGF plasma levels were analyzed in a subgroup of 23 healthy men aged 18-36 years.


RESULTS
Three novel mutations (702 C/T, 936 C/T, 1612 G/A) were found, allele frequencies of 702T, 936T and 1612A were of 0.017, 0.160 and 0.471, respectively. VEGF plasma levels were significantly lower in carriers of the 936T allele (9.1 +/- 2.7 pg/ml, mean +/- SEM) than in noncarriers (28.0 +/- 5.5 pg/ml, p = 0.033), whereas the 702 C/T and the 1612 G/A mutations showed no association with VEGF plasma levels. The 936 C/T exchange led to the loss of a potential binding site for transcription factor AP-4, although the functionality of this binding site remains unclear.


CONCLUSIONS
We have found three common mutations in the VEGF gene; one of them, a 936 C/T exchange, may be an important determinant of VEGF plasma levels.
Renner
W
W
Department of Internal Medicine, Division of Angiology, Karl-Franzens University Graz, Graz, Austria. wilfried.renner@kfunigraz.ac.at
Kotschan
S
S
Hoffmann
C
C
Obermayer-Pietsch
B
B
Pilger
E
E
D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D001665:Binding Sites; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000097:blood / Q000235:genetics*; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005796:Genes; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008222:Lymphokines / Q000097:blood / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C055473:enhancer-binding protein AP-4