Association between rheumatoid arthritis and polymorphism of tumor necrosis factor receptor II, but not tumor necrosis factor receptor I, in Caucasians

Abstract

Objective Tumor necrosis factor (TNF) is a powerful mediator of inflammation in rheumatoid arthritis (RA). In vivo, its acute effects are limited by binding to soluble receptors (TNFR), suggesting that TNFR genes could be important candidate risk factors. The present study was undertaken to investigate association of polymorphisms of TNFRI and TNFRII with RA in subjects in the UK. Methods Unrelated Caucasian RA patients (n = 291) and healthy Caucasian controls (n = 143) were genotyped for A/G polymorphism in exon 1 of TNFRI. From this sample, 240 of the patients and 137 controls were also typed for a single‐nucleotide polymorphism (SNP) in exon 6 of the TNFRII gene. In followup studies, DNA samples from UK Caucasian RA patients with a positive family history (n = 149) and UK Caucasian patients with sporadic RA (n = 208) were also typed for the exon 6 TNFRII polymorphism. Results TNFRI polymorphism was not associated with RA (odds ratio [OR] for GG genotype 0.93, 95% confidence interval [95% CI] 0.54–1.60). For TNFRII, in the initial study group, patients with RA were significantly more likely to be positive for both the G allele and GG genotype than were controls (OR for GG genotype 2.55, 95% CI 1.11–5.86). The association appeared to be confined to those with a family history of RA. This finding was replicated in an independent cohort of patients with familial RA. Conclusion The results of this study provide evidence of association between an SNP in the TNFRII gene and RA, the strongest association being observed in patients with a family history. No evidence of association between RA and TNFRI was demonstrated.

Dense genome‐wide linkage analysis of rheumatoid arthritis, including covariates

“…Work on the development of a new bioinformatics tool that will help in ranking of candidate genes, to provide detailed information about the candidate genes lying on the 19 suggested regions, is ongoing. Obvious candidates in the 19 regions should be investigated first, such as PADI4 on chromosome 1, recently identified in the Japanese population (37), TNFR2 on chromosome 1 (38,39), and RANK on chromosome 18 (8). The Japanese investigators have also recently reported a new RA "susceptibility" gene, SLC22A4 (organic cation transporter) on 5q31 (40), located 20 cM 5Ј to our chromosome 5 suggested locus.…”

Gene–gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis

“…Previous studies demonstrated a potential involvement of TNFRSF1B( þ 196) with systemic diseases, such as Crohn's disease, 36 systemic lupus erythematosus 37 and rheumatoid arthritis. 38 These inflammatory diseases seem to share a common pathogenetic pathway, with destructive periodontal disease; however, no studies have been focused on the role of this gene in the susceptibility for periodontal disease.…”

Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

“…Despite numerous data at the protein and cellular level implicating these cytokines in RA pathogenesis, genetic polymorphism analyses and their functional consequences have proven contradictory. [9][10][11][12][13] We have speculated that cytokine genes that regulate a Th1 dominant pathway may associate with RA. In particular, we have focused on the innate response cytokine interleukin (IL)-18.…”