title: Antinuclear antibodies are associated with tumor necrosis factor receptor I gene polymorphism in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Antinuclear antibodies (ANA) are a common feature of autoimmune diseases such as rheumatoid arthritis (RA). Herein, we investigate the relationship between ANA and polymorphism in the tumour necrosis factor receptor (TNFR) genes.
  
  
  METHODS
  Serum titers of ANA at diagnosis were measured in 267 patients with RA and a single nucleotide polymorphism (SNP) in each of the TNFR-I (36A/G) and TNFR-II (676T/G) genes was genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Circulating levels of soluble TNFR (sTNFR) and TNF-α were also measured in some patients.
  
  
  RESULTS
  Our initial analyses revealed the presence of ANA was associated with the TNFR-I 36A/G SNP, with a trend of increasing ANA frequency with G allele dosage (p=0.004). ANA status was also associated with lower sTNFR-I levels and a raised sTNFR-II/sTNFR-I ratio. The TNFR-II 676T/G SNP and circulating levels of sTNFR-II and TNF-α were not associated with ANA status. In an adjusted multivariate regression model the TNFR-I 36 GG genotype (OR 7.8, p=0.008) and levels of sTNFR-I (p=0.018) were independently associated with ANA status.
  
  
  CONCLUSIONS
  Our findings suggest a possible link between the production of ANA and the TNF-α/TNFR-I signalling system, which may be related to the apoptosis-inducing ability of this cytokine.
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire, United Kingdom. j.r.glossop@keele.ac.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Glossop
authors.forename: P T
authors.initials: PT
authors.lastname: Dawes
authors.forename: D L
authors.initials: DL
authors.lastname: Mattey
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004739:England; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506235:TNFRSF1A protein, human; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha