Christopher Butt

VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis

BackgroundAngiogenesis 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.MethodsTwo 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 Fishers 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.ResultsWe have observed an increased frequency in the T allele of VEGF +936 (rs3025039) in control subjects when compared to our PsA patients [Fishers exact p-value = 0.042; OR 0.653 (95% CI: 0.434, 0.982)]. Haplotyping of markers revealed no significant associations.ConclusionThe 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.

TNFα polymorphisms and risk of psoriatic arthritis

Background: Tumour necrosis factor α (TNFα) is a cytokine of critical importance in psoriatic arthritis. Objectives: (1) To examine the association between TNFα promoter gene polymorphisms and psoriatic arthritis in two well characterised Canadian populations with the disease; (2) to carry out a meta-analysis of all TNFα association studies in white psoriatic arthritis populations. Methods: DNA samples were genotyped for five TNF variants by time of flight mass spectrometry using the Sequenom platform. All five single nucleotide polymorphisms were in the 5′ flanking region of TNFα gene at the following positions: −1031 (T→C), −863 (C→A), −857 (C→T), −308 (G→A), and −238 (G→A). Primary analyses were based on logistic regression. Summary estimates of disease/genotype relations from several studies were derived from random effects meta-analyses. Results: 237 psoriatic arthritis subjects and 103 controls from Newfoundland and 203 psoriatic arthritis subjects and 101 controls from Toronto were studied. A combined analysis of data from both populations, showed a significant association between disease status and the −238(A) variant (p = 0.01). The meta-analysis estimate for the −238(A) TNFα variant in eight psoriatic arthritis populations was also significant (odds ratio = 2.29 (95% confidence interval, 1.48 to 3.55)). Conclusions: Analysis of TNFα variants in psoriatic arthritis populations shows that the −238 (A) variant is a significant risk factor for this disease.

Association of functional variants of PTPN22 and tp53 in psoriatic arthritis: a case-control study

Recent studies have implicated PTPN22 and tp53 in susceptibility to several autoimmune diseases, including rheumatoid arthritis, suggesting that these genes are important in maintaining immune homeostasis. Because autoimmune diseases may share similar susceptibility loci, investigation of these genes in psoriatic arthritis (PsA) is of potential relevance. As a result we investigated known coding polymorphisms in PTPN22 and tp53 in a homogenous Caucasian PsA cohort from Newfoundland, Canada and an admixed Caucasian PsA cohort from Toronto, Canada. We observed a moderate association of the R620W variant of PTPN22 with PsA in the Toronto population only. Because of the conflicting findings reported regarding the association of PTPN22 with PsA, further studies in other PsA populations are warranted.