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Antinuclear antibodies are associated with tumor necrosis factor receptor I gene polymorphism in patients with rheumatoid arthritis


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CER4340
2011 Vol.29, N°4
PI 0609, PF 0615
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PMID: 21813053 [PubMed]

Received: 29/11/2010
Accepted : 14/02/2011
In Press: 31/08/2011
Published: 30/08/2011

Abstract

OBJECTIVES:
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.

Rheumatology Article