TNF-β +252 A>G (rs909253) polymorphism is independently associated with presence of autoantibodies in rheumatoid arthritis patients

• Published in: Clinical and experimental medicine 2019-08, Vol.19 (3), p.347-356
• Main Authors: de Medeiros, Fabiano Aparecido, Alfieri, Daniela Frizon, Iriyoda, Tatiana Mayumi Veiga, Costa, Neide Tomimura, de Almeida, Elaine Regina Delicato, Lozovoy, Marcell Alysson Batisti, Mari, Naiara Lourenço, Flauzino, Tamires, Reiche, Edna Maria Vissoci, Dichi, Isaias, Simão, Andréa Name Colado
• Format: Article
• Language: English
• Subjects: Alleles; Autoantibodies; Citrulline; Gene frequency; Gene polymorphism; Hematology; Inflammation; Internal Medicine; Medicine; Medicine & Public Health; Oncology; Original Article; Plasma levels; Polymerase chain reaction; Polymorphism; Restriction fragment length polymorphism; Rheumatoid arthritis; Rheumatoid factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1591-8890; 1591-9528
• DOI: 10.1007/s10238-019-00556-9

The TNF-β +252 A>G (rs909253) polymorphism has been associated with a risk of development of rheumatoid arthritis (RA) and could influence plasma tumor necrosis factor alpha (TNF-α) levels. The aim of the present study was to evaluate the association between the TNF-β +252 A>G polymorphism with plasma TNF-α levels, the presence of autoantibodies, and the susceptibility for RA. This cross-sectional study included 261 patients with RA and 292 controls. The polymorphism was studied using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Soluble TNF-α and receptors swere measured by multiplex assay. Rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) were measured using immunoassay. No differences were observed in allele frequency and genotype distribution among patients and controls. The presence of RF ( p  = 0.020) and anti-CCP ( p  = 0.001) increased 4.23-fold and 8.13-fold, respectively, in patients with B1 allele (B1/B2 + B1/B1 genotypes) independently of demographic, clinical, and inflammatory markers. Among patients with B1/B2 + B1/B1 genotypes, higher TNF-α levels were associated with positive RF ( p  = 0.040), anti-CCP ( p  = 0.011), or both ( p  = 0.038). In patients carrying B1 allele, the increased sTNFR1 together with RF or anti-CCP or both explained about 39.0% the variations in TNF-α level. However, in B2/B2 genotype, the presence of those autoantibodies was not associated with TNF-α level. Our findings indicate that the TNF-β +252 A>G polymorphism was not associated with RA susceptibility and TNF-α plasma levels. However, B1 allele was associated with the presence of autoantibodies. In addition, interaction between the presence of B1 allele and autoantibodies was associated with the increase of plasma TNF-α level in RA patients.