Expression of the autoimmunity associated TNFAIP3 is increased in rheumatoid arthritis but does not differ according to genotype at 6q23

Maxwell, James R.; Gowers, Isobel; Kuet, Kar-Ping; Barton, Anne; Worthington, Jane; Wilson, Anthony G.

doi:10.1093/rheumatology/kes134

Cited by 13 publications

(12 citation statements)

References 9 publications

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“…We finally identified 21 studies (27,451 cases and 30,443 controls) in this meta-analysis. 14 studies [9–13, 18, 20, 21, 23, 26–29] with 21,040 cases and 23,086 controls examined rs6920220 polymorphism; 6 studies [14, 17, 19, 22, 24, 25] including 5,912 cases and 6,463 controls investigated rs2230926 polymorphism; 5 studies [16, 18, 21, 23, 24] involving 12,518 cases and 14,061 controls explored rs5029937 polymorphism. The characteristics of included studies were summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis

Shen

Ruan²,

et al. 2017

Oncotarget

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Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. To date, many studies explored the associations between tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs6920220, rs2230926, and rs5029937 polymorphisms and the risk of rheumatoid arthritis (RA), but with contradictory results. We therefore conducted a comprehensive meta-analysis to address the associations. We searched in the databases of PubMed and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Stata 11.0 software. A total of 21 case-control studies for these three single nucleotide polymorphisms (SNPs) were included in this meta-analysis. Meta-analysis indicated that TNFAIP3 gene rs6920220, rs2230926, and rs5029937 polymorphisms were associated with the increased risk of RA. Stratification analysis of ethnicity found that rs6920220 and rs5029937 polymorphisms increased the risk of RA among Caucasians, while rs2230926 polymorphism increased the risk of RA among Asians. In summary, this meta-analysis confirms that TNFAIP3 gene polymorphisms may play important roles in the pathogenesis of RA.

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Section: Resultsmentioning

confidence: 99%

Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis

Shen

Ruan²,

et al. 2017

Oncotarget

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“…One reason may be polymorphisms of the TNFAIP3 gene (18,19). In peripheral blood cells, no significant difference was detected in TNFAIP3 expression according to genotype at the intergenic markers rs6920220 and rs13207033 in RA patients or controls (37). For rs5029937 and rs7749323, TNFAIP3 expression was reduced in RA patients carrying the risk allele compared with G/G in controls (37).…”

Section: Discussionmentioning

confidence: 83%

“…In peripheral blood cells, no significant difference was detected in TNFAIP3 expression according to genotype at the intergenic markers rs6920220 and rs13207033 in RA patients or controls (37). For rs5029937 and rs7749323, TNFAIP3 expression was reduced in RA patients carrying the risk allele compared with G/G in controls (37). For rs5029937 and rs7749423, the trend demonstrated that TNFAIP3 expression was reduced in healthy controls, suggesting a possible small allele-specific effect on TNFAIP3 expression (37).…”

Section: Discussionmentioning

confidence: 89%

“…For rs5029937 and rs7749323, TNFAIP3 expression was reduced in RA patients carrying the risk allele compared with G/G in controls (37). For rs5029937 and rs7749423, the trend demonstrated that TNFAIP3 expression was reduced in healthy controls, suggesting a possible small allele-specific effect on TNFAIP3 expression (37). Therefore, the difference of TNFAIP3 expression may be partially attributed to polymorphism of the TNFAIP3 gene.…”

Section: Discussionmentioning

confidence: 95%

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Altered TNFAIP3 mRNA expression in peripheral blood mononuclear cells from patients with rheumatoid arthritis

et al. 2015

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Abstract. The tumor necrosis factor α-induced protein-3 (TNFAIP3) gene functions in negative immunoregulation and its single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA) disease. However, its expression level in immune cells from RA patients remains unclear. The aim of the present study was to investigate whether the expression of TNFAIP3 is changed in patients with RA. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine TNFAIP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls. TNFAIP3 expression was decreased in RA patients compared with the healthy controls. The expression level of the TNFAIP3 gene negatively correlated with the RA score, anti-cyclic citrullinated peptide (CCP) antibody levels and C-reactive protein levels. Furthermore, RA patients with positive results of anti-CCP antibodies had a lower expression of TNFAIP3 than those without anti-CCP antibodies. In conclusion, the present results suggest that the insufficient expression of the TNFAIP3 gene in PBMCs may correlate with the diagnosis of RA. IntroductionRheumatoid arthritis (RA) is a common chronic inflammatory disease that predominantly affects the small joints of the hands and feet (1). The propagation of inflammation is characterized by migration of mononuclear cells into the local inflammatory sites, leading to the hyperplasia of fibroblast-like synoviocytes (FLSs) primarily due to resistance to apoptosis and damage to cartilage and bone (2). The chronic inflammation is attributed to breakdown of immune homostasis, which results in activation of immune cells and elevation of pro-inflammatory cytokines (3). The immune activation leads to deposition of immune complexes and mononuclear cell infiltration into susceptible organs, while the pro-inflammatory cytokines are responsible for maintenance of the immune activation (4). The major mediators of chronic inflammation in RA include tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-8 and prostaglandin E2 (5). Induction of pro-inflammatory mediators requires activation of the nuclear factor (NF)-κB inducing kinase-or inhibitor of NF-κB (IκB) kinase-mediated NF-κB signal transduction pathways (6,7). The transcription factor NF-κB has been well recognized as a key regulator of inflammation in RA (8-10).TNF-α-induced protein-3 (TNFAIP3) is an important negative immunoregulatory gene. TNFAIP3 is a dual ubiquitin-editing enzyme, whose expression is induced by a large number of stimuli in a wide variety of cells (11). Evidence from animal models indicates that TNFAIP3 is a plausible candidate gene in RA susceptibility (11). In TNFAIP3 knockout mice, its deficiency leads to death shortly following birth by severe inflammation and tissue damage in multiple organs (12,13). In immune cells, overexpression of TNFAIP3 can terminate NF-κB signaling transduced from TNF receptors, toll-like receptors, nucleotide-binding oligomerization domain containing 2 receptors or T ...

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“…A study from UK [15] found rs13207033 polymorphism was significantly associated with a decreased risk of RA, but the remaining five studies [10, 11, 14, 17, 21] did not replicate the association. Therefore, we conducted the meta-analysis to demonstrate this SNP with RA risk.…”

Section: Discussionmentioning

confidence: 99%

TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of rheumatoid arthritis

et al. 2016

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Accumulating evidences suggested that tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs10499194, rs13207033 polymorphisms may be associated with the risk of rheumatoid arthritis (RA). However, these studies yielded contradictory findings. To clarify convincing associations, we conducted a comprehensive meta-analysis by searching in PubMed, Embase, and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 13 case-control studies for rs10499194 polymorphism and 6 studies for rs13207033 polymorphism were included. Our data indicated that TNFAIP3 gene rs10499194, rs13207033 polymorphisms were associated with the decreased risk of RA. Stratification analyses of ethnicity indicated rs10499194, rs13207033 polymorphisms decreased the risk of RA among Caucasian populations, but not among Asian populations. In conclusion, this meta-analysis indicates that TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of RA, especially among Caucasian populations.

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Expression of the autoimmunity associated TNFAIP3 is increased in rheumatoid arthritis but does not differ according to genotype at 6q23

Cited by 13 publications

References 9 publications

Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis

Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis

Altered TNFAIP3 mRNA expression in peripheral blood mononuclear cells from patients with rheumatoid arthritis

TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of rheumatoid arthritis

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