A Functional Variant of Vascular Endothelial Growth Factor Is Associated with Severe Ischemic Complications in Giant Cell Arteritis

BLANCA RUEDA, MIGUEL A. LOPEZ-NEVOT, MARIA J. LOPEZ-DIAZ, CARLOS GARCIA-PORRUA, JAVIER MARTÍN, and MIGUEL A. GONZALEZ-GAY

ABSTRACT.

Objective. Angiogenesis, the formation of new blood vessels, may play a role in giant cell arteritis (GCA), the most common type of systemic vasculitis in the elderly in Western countries. Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic mediators. We wanted to assess the potential role of –1154 G→A (rs1570360) and –634 G→C (rs2010963) VEGF gene functional variants in GCA susceptibility and clinical ischemic complications.

Methods. One hundred and three patients with biopsy-proven GCA and 226 ethnically matched controls from the Lugo region (Northwest Spain) were genotyped for the VEGF –1154 G→A and –634 G→C polymorphisms using a real time polymerase chain reaction technology based on TaqMan 5' allelic discrimination assay.

Results. No significant differences in allele or genotype frequencies for the 2 VEGF polymorphisms were observed between patients and controls. However, the VEGF –634 G allele was significantly more frequent among GCA patients with severe ischemic complications compared with GCA patients not affected by ischemic events (p = 0.017, odds ratio, OR: 2.05; 95% confidence interval, CI: 1.13–3.71; p_c = 0.034) or with controls (p = 0.021, OR: 1.75; 95% CI: 1.08–2.88; p_c = 0.042). In this regard, the carriage rate of the risk allele G showed statistically significant skewing comparing GCA patients with severe ischemic events with the remaining GCA patients (GG + GC vs CC: p = 0.009, OR: 5.26; 95% CI: 1.39–19.98; p_c= 0.018).

Conclusion. Our results suggest a potential implication of the VEGF gene –634 G→C polymorphism in the development of severe ischemic manifestations of GCA. (J Rheumatol 2005;32:1737-41)

Key Indexing Terms:

GIANT CELL (TEMPORAL) ARTERITIS
TEMPORAL ARTERY BIOPSY
VASCULAR ISCHEMIC COMPLICATIONS
GENE POLYMORPHISMS
VASCULAR ENDOTHELIAL GROWTH FACTOR
VEGF

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From the Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC and the Division of Immunology, Hospital Virgen de las Nieves, Granada; and the Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain.

Supported by grant SAF03-3460 from Plan Nacional de I+D+I and in part by Junta de Andalucía, grupo CTS-180.

B. Rueda, PhD; J. Martin, Instituto de Parasitologia y Biomedicina Lopez-Neyra; CSIC; M.A. Lopez-Nevot, MD, PhD, Division of Immunology, Hospital Virgen de las Nieves; M.J. Lopez-Diaz, MD; C. Garcia-Porrua, MD, PhD; M.A. Gonzalez-Gay, MD, PhD, Division of Rheumatology, Hospital Xeral-Calde.

Dr. Gonzalez-Gay and Dr. Martin share senior authorship of this report.

Address reprint requests to Dr. M.A. Gonzalez-Gay, Rheumatology Division, Hospital Xeral-Calde, c) Dr. Ochoa s/n, 27004, Lugo, Spain. E-mail:miguelaggay@hotmail.com

Accepted for publication May 9, 2005.

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