A functional variant of vascular endothelial growth factor is associated with severe ischemic complications in giant cell arteritis.
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; pc = 0.034) or with controls (p = 0.021, OR: 1.75; 95% CI: 1.08-2.88; pc = 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; pc= 0.018).


CONCLUSIONS
Our results suggest a potential implication of the VEGF gene -634 G-->C polymorphism in the development of severe ischemic manifestations of GCA.
Rueda
Blanca
B
Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC.
Lopez-Nevot
Miguel A
MA
Lopez-Diaz
Maria J
MJ
Garcia-Porrua
Carlos
C
Martín
Javier
J
Gonzalez-Gay
Miguel A
MA
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D013700:Giant Cell Arteritis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013699:Temporal Arteries; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A