The −383A>C TNFRI polymorphism is associated with soluble levels and clinical activity in rheumatoid arthritis

Abstract

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in inflammation, and it has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). TNF-alpha activity is mediated through TNFRI and TNFRII cell surface receptors, which act as physiological attenuators of TNF-alpha activity. We recruited 190 RA patients and 190 healthy subjects (HS) in order to associate the -383A>C TNFRI polymorphism with sTNFRI levels and DAS28 score in RA. In results, sTNFRI levels were higher in RA patients than HS (P = 0.04). The -383A>C TNFRI polymorphism did not show significant differences in both studied groups. However, in the RA group the sTNFRI levels were significantly elevated (P = 0.004) in A/A genotype carriers. In addition, the A/A genotype carriers had the higher DAS28 score than A/C genotype (P = 0.02). These data suggest that -383A>C TNFRI polymorphism is not a susceptibility marker in RA, whereas the increased levels of sTNFRI could reflect the clinical activity in RA patients.

TNFR1-383 A˃C polymorphism association with clinical manifestations in primary Sjögren’s syndrome patients

“…TNFR1 is a molecule that can initiate the extrinsic apoptosis pathway and has been reported to be elevated in the peripheral blood of patients with rheumatic diseases such as AS and SLE (Derréet al, 1991;Szodoray et al, 2004;Valle et al, 2010;Corona-Sanchez et al, 2012).…”

“…Amplification was performed using the following primers: forward 5'-TTATTGCCCCTTG-GTGTTTGGTTG-3' and reverse 5'-GAGGGGAAGAGTGAGGCAGTGTT-3' (Pitts et al, 1998;Wu et al, 2004;Valle et al, 2010;Corona-Sanchez et al, 2012). The polymerase chain reaction (PCR) reaction was performed in a 50-µL final volume containing 1 µL gDNA, 3 µM each primer, 1.25 U/µL Taq DNA polymerase (Invitrogen, Carlsbad, CA, USA), 5 µL supplied 10X Taq reaction buffer using a 1X concentration for each PCR reaction (Invitrogen, Carlsbad, CA, USA), 1 mM MgCl 2 , and 0.1 mM each dNTP (Invitrogen, Carlsbad, CA, USA).…”

“…The PCR was performed by initial denaturation at 94°C for 3 min, followed by 35 amplification cycles at the following conditions: 94°C for 1 min for denaturalitation, an annealing step at 62°C for 30 s, and an extension at 72°C for 1 min, and a final extension at 72°C in a Techne thermocycler (Model T-412; LabTech, Tampa, FL, USA). The final PCR product was a 199-bp fragment that was digested with 10 U BglII enzyme (Pitts et al, 1998;Wu et al, 2004;Valle et al, 2010;Corona-Sanchez et al, 2012) (New England BioLabs, Beverly, MA, USA) in the thermocycler for 4 h at 37°C. The wild-type genotype (A˃A) corresponds to 135-and 64-bp fragments, the heterozygote genotype (A˃C) is represented by the 199-, 135-, and 64-bp fragments, and the homozygote polymorphic genotype (C˃C) corresponds to the 199-bp fragment.…”

“…Apoptosis plays an important role in this disease by interacting with pro-inflammatory molecules such as tumor necrosis factor alpha (TNFα) (Hohmann et al, 1989;Lobito et al, 2006) and has a pleiotropic effect after binding to its transmembrane receptor (tumor necrosis factor receptor-1, TNFR1, or TNFR2) (Valle et al, 2010) that initiates apoptosis through the extrinsic pathway (Beg et al, 1996;Cope et al, 1997;Xanthoulea et al, 2004). Apoptosis is increased in chronic inflammatory diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and pSS (Bayley et al, 2003;Szodoray et al, 2004;Valle et al, 2010;Corona-Sanchez et al, 2012).…”

“…Apoptosis is increased in chronic inflammatory diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and pSS (Bayley et al, 2003;Szodoray et al, 2004;Valle et al, 2010;Corona-Sanchez et al, 2012).…”