Vascular endothelial growth factor gene polymorphisms in Behçet's disease.
OBJECTIVE
To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Behçet's disease (BD) and disease expression.


METHODS
Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs3025039) and -634 C/G (rs2010963) mutations and for an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in healthy controls homozygous for the polymorphisms studied.


RESULTS
The carriage rates of the alleles I and -634C were significantly more frequent in patients with BD than in healthy controls [p corr = 0.036, OR 1.8 (95% CI 1.1-2.9) and p corr = 0.05, OR 1.8 (95% CI 1.1-3.0), respectively]. While the distribution of allele +936T was similar in patients with BD and healthy controls, its frequency was significantly higher in BD patients with posterior uveitis/retinal vasculitis than in those without (p = 0.022, OR 2.4, 95% CI 1.1-5.0). Lipopolysaccharide-stimulated VEGF production from PBMC of healthy subjects was higher in II homozygous than in DD homozygous.


CONCLUSIONS
Our data indicate that carriers of -634C and I alleles are associated with susceptibility to developing BD.
Salvarani
Carlo
C
Unità di Reumatologia and Laboratorio di Biologia Molecolare, Ospedale di Reggio Emilia, Bologna, Italy. salvarani.carlo@asmn.re.it
Boiardi
Luigi
L
Casali
Bruno
B
Olivieri
Ignazio
I
Cantini
Fabrizio
F
Salvi
Fabrizio
F
Malatesta
Renato
R
La Corte
Renato
R
Triolo
Giovanni
G
Ferrante
Angelo
A
Filippini
Davide
D
Paolazzi
Giuseppe
G
Sarzi-Puttini
Piercarlo
P
Nicoli
Davide
D
Farnetti
Enrico
E
Chen
Qingquan
Q
Pulsatelli
Lia
L
D000293:Adolescent; D000328:Adult; D001528:Behcet Syndrome / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D008297:Male; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A