VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis.
BACKGROUND
Angiogenesis appears to be a first-order event in psoriatic arthritis (PsA). Among angiogenic factors, the cytokines vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and fibroblast growth factors 1 and 2 (FGF1 and FGF2) play a central role in the initiation of angiogenesis. Most of these cytokines have been shown to be upregulated in or associated with psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). As these diseases share common susceptibility associations with PsA, investigation of these angiogenic factors is warranted.


METHODS
Two hundred and fifty-eight patients with PsA and 154 ethnically matched controls were genotyped using a Sequenom chip-based MALDI-TOF mass spectrometry platform. Four SNPs in the VEGF gene, three SNPs in the EGF gene and one SNP each in FGF1 and FGF2 genes were evaluated. Statistical analysis was performed using Fisher's exact test, and the Cochrane-Armitage trend test. Associations with haplotypes were estimated by using weighted logistic models, where the individual haplotype estimates were obtained using Phase v2.1.


RESULTS
We have observed an increased frequency in the T allele of VEGF +936 (rs3025039) in control subjects when compared to our PsA patients [Fisher's exact p-value = 0.042; OR 0.653 (95% CI: 0.434, 0.982)]. Haplotyping of markers revealed no significant associations.


CONCLUSIONS
The T allele of VEGF in +936 may act as a protective allele in the development of PsA. Further studies regarding the role of pro-angiogenic markers in PsA are warranted.
Butt
Christopher
C
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada. cbutt@mun.ca <cbutt@mun.ca>
Lim
Sooyeol
S
Greenwood
Celia
C
Rahman
Proton
P
D000328:Adult; D015535:Arthritis, Psoriatic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004815:Epidermal Growth Factor / Q000235:genetics; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007596:Joints / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor