Abstract: Vascular Endothelial Growth Factor Gene Polymorphisms in Giant Cell Arteritis

Vascular Endothelial Growth Factor Gene Polymorphisms in Giant Cell Arteritis

LUIGI BOIARDI, BRUNO CASALI, DAVIDE NICOLI, ENRICO FARNETTI, QINGQUAN CHEN, PIERLUIGI MACCHIONI, MARIA GRAZIA CATANOSO, LIA PULSATELLI, RICCARDO MELICONI, and CARLO SALVARANI

ABSTRACT.

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.

Conclusion. Our data indicate that carriers of C634 and I alleles are associated with susceptibility to developing GCA. (J Rheumatol 2003;30:2160-4)

Key Indexing Terms:

GIANT CELL ARTERITIS
VASCULAR ENDOTHELIAL GROWTH FACTOR
POLYMORPHISMS
VEGF PRODUCTION
ISCHEMIC MANIFESTATIONS

From the Servizio di Reumatologia and Laboratorio di Biologia Molecolare, Azienda Ospedaliera Arcispedale S. Maria Nuova, Reggio Emilia; Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna; and Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, University of Bologna, Bologna, Italy.

L. Boiardi, MD, PhD; P. Macchioni, MD; M.G. Catanoso, MD; C. Salvarani, MD, Servizio di Reumatologia; B. Casali, MD; D. Nicoli, BD; E. Farnetti, BD; Q. Chen, MD, Laboratorio di Biologia Molecolare, Azienda Ospedaliera Arcispedale S. Maria Nuova; L. Pulsatelli, BD, Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli; R. Meliconi, MD, Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli and Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, University of Bologna.

Address reprint requests to Dr. C. Salvarani, Servizio di Reumatologia, Arcispedale S. Maria Nuova, V. le Umberto 1 N50, 42100 Reggio Emilia, Italy. E-mail: salvarani.carlo@asmn.re.it

Submitted October 17, 2002; revision accepted February 10, 2003.