Abstract
To observe and evaluate the correlation between single-nucleotide polymorphisms (SNPs) and messenger RNA (mRNA) level related to tristetraprolin (TTP) in Chinese rheumatoid arthritis (RA). TapMan SNP was used for genotyping analysis in 580 RA patients and 554 healthy people. Association between TTP gene polymorphisms (rs251864 and rs3746083) and RA was obtained. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) technology was applied for the detection of TTP mRNA level in peripheral blood mononuclear cells (PBMCs) in 36 RA patients and 37 healthy people. We observed that the allele T of TTP rs3746083 increased RA susceptibility (p = 0.019). A significant difference was found under the dominant model of rs3746083 (p = 0.037). Further analysis showed the allele distribution of rs3746083 was nominally correlated with RF phenotype of RA patients (p = 0.045). Nevertheless, the association between TTP rs251864 and the incidence of RA was no statistically significant (p > 0.05). The TTP expression level in PBMCs of RA patients was significantly reduced (p < 0.001). In conclusion, the results of this experiment support that TTP may be involved in the pathogenesis of RA.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by autoantibody production, persistent inflammatory synovitis and progressive destruction of articular cartilage and bone (Jiang et al, 2014)
We evaluated the associations of rs251864 and rs3746083 SNPs with rheumatoid factor (RF) and anti-cyclic citrullinated peptide in rheumatoid arthritis (RA) patients (Table 3)
The results showed that TTP messenger RNA (mRNA) level in RF-negative patients decreased statistically (Z −1.975, p 0.048; Figure 3)
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by autoantibody production, persistent inflammatory synovitis and progressive destruction of articular cartilage and bone (Jiang et al, 2014). The decay of messenger RNA (mRNA) is associated with many inflammation-related gene expression regulation mechanisms. Tristetraprolin (TTP) as a RNA-binding protein has been well characterized. TTP-deficient mice exhibited systemic autoimmune inflammatory symptoms consisting of erosive arthritis, cachexia, conjunctivitis, dermatitis and glomerular mesangial thickening (Taylor et al, 1996). TTP contribute to regulate the expression of pro-inflammatory gene through its mRNA-decay function, and participate in the regulation of inflammatory signal transduction. Taking together these findings, it suggests that TTP may be involved in the pathogenesis of RA. The TTP mRNA level in peripheral blood mononuclear cells (PBMCs) was evaluated
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