Vascular endothelial growth factor gene polymorphisms in giant cell arteritis.
OBJECTIVE
To examine potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with giant cell arteritis (GCA) and disease expression, in particular in patients with and without ischemic complications.


METHODS
We enrolled 92 consecutive patients with biopsy-proven GCA residing in Reggio Emilia, Italy. Two hundred healthy blood donors from the same geographic area were selected as controls. All the GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for 936 C/T and 634 C/G mutations and for an 18 bp insertion/deletion (I/D) polymorphism in the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in controls homozygous for the polymorphisms studied.


RESULTS
The carriage rates of the alleles I and C634 were significantly more frequent in GCA patients than in controls (p = 0.025, OR 1.9, 95% CI 1.1-3.1 and p = 0.015, OR 2.1, 95% CI 1.1-3.6, respectively). The distribution of allele T936 was similar in GCA patients and controls. No significant differences in the distribution of the polymorphisms studied were observed in patients with ischemic manifestations compared to those without ischemic manifestations. Lipopolysaccharide (LPS)-stimulated VEGF production by PBMC from controls was higher in II homozygous compared to DD homozygous patients.


CONCLUSIONS
Our data indicate that carriers of C634 and I alleles are associated with susceptibility to developing GCA.
Boiardi
Luigi
L
Servizio di Reumatologia and Laboratorio di Biologia Molecolare, Azienda Ospedaliera Arcispedale S. Maria Nuova, Viale Umberto 1 N50, 42100 Reggio Emilia, Italy.
Casali
Bruno
B
Nicoli
Davide
D
Farnetti
Enrico
E
Chen
Qingquan
Q
Macchioni
Pierluigi
P
Catanoso
Maria Grazia
MG
Pulsatelli
Lia
L
Meliconi
Riccardo
R
Salvarani
Carlo
C
D000368:Aged; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D020022:Genetic Predisposition to Disease; D013700:Giant Cell Arteritis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D008070:Lipopolysaccharides; D042461:Vascular Endothelial Growth Factor A; D004247:DNA