The role of vascular endothelial growth factor (VEGF) in inflammatory bowel disease.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a candidate susceptibility gene to inflammatory bowel disease (IBD), both from a functional as well as genetic perspective. Moreover, serum VEGF (sVEGF) levels are increased in IBD and correlate with disease activity. Both VEGF expression and sVEGF levels may be influenced by VEGF gene polymorphisms.


OBJECTIVE
To study VEGF polymorphisms in IBD susceptibility and their impact on sVEGF levels.


METHODS
Four functional VEGF polymorphisms (-C2578A, -G1154A, -G634C, and C936T) were genotyped in two independent cohorts (cohort 1: 372 IBD trios; cohort 2: 452 unrelated IBD patients, 271 healthy controls [HC]; and 93 patients with non-IBD gastrointestinal inflammation [non-IBD GI]), using polymerase chain reaction with restriction fragment length polymorphism and TaqMan minor groove binding. Phenotypical data on all patients as well as sVEGF levels were correlated with the genetic data.


RESULTS
Both the VEGF genotype and haplotype frequencies did not differ between IBD patients and controls, and no distortion of transmission was observed. sVEGF levels were increased in IBD but also in non-IBD GI patients, compared with HC, and were only influenced by VEGF polymorphisms in patients with Crohn's disease (-G1154A genotype and -2578/-1154/-634 AAG promoter haplotype).


CONCLUSIONS
The VEGF polymorphisms studied are not implicated in susceptibility to IBD and do not predict sVEGF levels. Although increased sVEGF and angiogenesis are important features of IBD, they do not appear genetically determined.
Ferrante
Marc
M
Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
Pierik
Marie
M
Henckaerts
Liesbet
L
Joossens
Marie
M
Claes
Karolien
K
Van Schuerbeek
Nele
N
Vlietinck
Robert
R
Rutgeerts
Paul
P
Van Assche
Gert
G
Vermeire
Severine
S
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A