Assessment of genetic polymorphisms within nuclear factor-κB signaling pathway genes in rheumatoid arthritis: Evidence for replication and genetic interaction

Zeng, Zhen; Sun, Qingqing; Zhang, Wei; Wen, Qin-Wen; Wang, Ting‐Hui; Qin, Wen; Xiao, Dongmei; Zhang, Zhen; Hua, Huang; Mo, Yijun; Wu, Xiudi; Cen, Han

doi:10.1016/j.intimp.2021.108089

Cited by 7 publications

(4 citation statements)

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“…TNIP1 encodes the protein ABIN1, which inhibits NF-kB signaling and plays a role in normal tissue homeostasis to prevent autoimmunity and inflammation [26]. Polymorphisms of TNIP1 have been associated with RA, as well as other polymorphisms of genes involved in nuclear factor-kB (NF-kB) signaling [27]. The increased expression of TNIP1 over time in our CSA-patients who did not progress to IA is in line with its anti-inflammatory role in the prevention of autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Cytokine and chemokine gene expression in patients with clinically suspect arthralgia; a longitudinal study during progression to inflammatory arthritis or non-progression

Heutz

Niemantsverdriet

Eeden

et al. 2022

Preprint

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Background: Autoantibody-responses rise years before onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and chemokine levels can also rise years before IA-onset, but the course after CSA-onset is unknown. To better understand the processes in this symptomatic at-risk phase, we studied the course of cytokine, chemokine and related receptors gene expression in CSA-patients during progression to IA, and in CSA-patients who ultimately did not develop IA. Differential expressed genes between ACPA-positive and ACPA-negative CSA-patients who developed IA were also explored. Methods: Whole blood RNA expression of 37 inflammatory cytokines/chemokines/related receptors was determined by dual-color reverse-transcription multiplex ligation-dependent probe amplification, in paired samples of CSA-patients at CSA-onset and either at IA-development or after 24-months without IA-development. ACPA-positive and ACPA-negative CSA-patients developing IA were compared at CSA-onset and during progression to IA. GEE-models tested changes over time. A false discovery rate approach was applied to correct for multiple testing. Results: None of the cytokines/chemokine genes significantly changed in expression between CSA-onset and IA-development. In CSA-patients without IA development, G-CSF expression decreased (p=0.001), whereas CCR6 and TNIP expression increased (p<0.001 and p=0.002, respectively) over a 2-year period. Expression levels in ACPA-positive and ACPA-negative CSA-patients who developed IA were similar. Conclusion: Whole blood gene expression of cytokines, chemokines and related receptors did not change significantly from CSA to IA-development. This suggests that changes in expression of these molecules occurred preceding CSA-onset and may not relate to the final hit of developing chronic arthritis. Observed changes in CSA-patients not developing IA can provide clues for processes related to resolution.

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Section: Discussionmentioning

confidence: 99%

Cytokine and chemokine gene expression in patients with clinically suspect arthralgia; a longitudinal study during progression to inflammatory arthritis or non-progression

Heutz

Niemantsverdriet

Eeden

et al. 2022

Preprint

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“…Five studies were excluded because they did not include data on TNFAIP3 polymorphisms or review articles. A total of 15 studies met the inclusion criteria [11][12][13][15][16][17][18][19][20][21][22][23][24][25][26] (Fig. 1).…”

Section: Studies Included In the Meta-analysismentioning

confidence: 99%

“…Several studies have examined the impact of TNFAIP3 polymorphisms on RA susceptibility [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. However, these investigations have shown conflicting results in various ethnicities.…”

Section: Introductionmentioning

confidence: 99%

Associations between TNFAIP3 Polymorphisms and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis Update with Trial Sequential Analysis

Lee

Song

2022

Public Health Genomics

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Introduction: The tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene produces ubiquitin-editing protein A20, which inhibits nuclear factor-κB (NF-κB) activation in a variety of signaling pathways. We examined the association between TNFAIP3 polymorphisms and rheumatoid arthritis (RA) susceptibility. Methods: MEDLINE, Embase, Scopus, and Web of Science were searched for available articles on TNFAIP3 polymorphisms in RA patients from inception until July 11, 2022. We included case-control studies on the association between rs2230926 and rs5029937 polymorphisms of TNFAIP3 and RA, and we excluded studies that contained overlapping data. We scored the quality of each study included based on the Newcastle-Ottawa Scale. Meta-analyses evaluated the association between TNFAIP3 polymorphisms and RA susceptibility in diverse ethnic populations and was verified through trial sequential analysis (TSA). This meta-analysis was registered in the PROSPERO register (number: CRD42022345160). There was no funding source. Results: Seventeen studies were chosen for meta-analysis. Ten studies for rs2230926, and seven for rs5029937. An association was noted between TNFAIP3 rs2230926 G allele and RA in all subjects (odds ratio [OR] = 1.389; 95% confidence interval [CI] = 1.161−1.662; p < 0.001). Ethnicity-specific analysis showed significant association of rs2230926 G allele with RA in Europeans and Asians (OR = 1.642; 95% CI = 1.099–2.452; p = 0.015; OR = 1.404; 95% CI = 1.262−1.562; p < 0.001). An association was also noted between TNFAIP3 rs5029937 T allele and RA in all subjects (OR = 1.389; 95% CI = 1.207−1.785; p < 0.001). An ethnicity-specific meta-analysis revealed a significant association of the rs5029937 T allele with RA in Europeans and Asians. Dominant model analysis showed the same pattern for TNFAIP3 rs2230926 G and rs5029937 T alleles in Europeans and Asians, suggesting an association between rs2230926 G and rs5029937. TSA indicated a robust association between the TNFAIP3 polymorphisms and the risk of RA. Conclusion: TNFAIP3 rs2230926 and rs5029937 polymorphisms are associated with RA susceptibility in European and Asian populations. However, the data were not stratified by parameters such as rheumatoid factor status, disease activity, or environmental variables.

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“…An increasing body of research has demonstrated the involvement of UBE2L3 in the pathogenesis of various diseases through the regulation of protein stability. These diseases include systemic lupus erythematosus (SLE) (Kim et al 2020 ; Mauro et al 2023 ), hepatitis B virus (HBV) infection (Zhou et al 2019 ), Alzheimer’s disease (AD) (Wei et al 2019 ), ischemic stroke (IS) (Wei et al 2019 ), celiac disease (CeD) (Fernandez-Jimenez and Bilbao 2019 ), and rheumatoid arthritis (RA) (Zeng et al 2021 ). Furthermore, it has been observed that UBE2L3 exhibits abnormally high expression in various human tumor types, indicating a potential role for UBE2L3 as an oncogene.…”

Section: Introductionmentioning

confidence: 99%

UBE2L3 expression in human gastric cancer and its clinical significance

Zhang,

Wei,

et al. 2024

J Cancer Res Clin Oncol

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Purpose Gastric cancer (GC) is prevalent as one of the most common malignant tumors globally, with a particularly high incidence in China. The role of UBE2L3 in the initiation and progression of various cancers has been well documented, but its specific significance in GC is not yet fully elucidated. The objective of this study is to examine the expression and importance of UBE2L3 in human gastric cancer tissues. Methods Immunohistochemical staining and survival analysis were conducted on 125 cases of GC. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to assess the expression of UBE2L3 in GC cell lines. Cell lines with UBE2L3 knockdown and overexpression were cultured through lentivirus transfection and subsequently assessed using Western blot analysis. The involvement of UBE2L3 in the proliferation, invasion, and apoptosis of GC cells was confirmed through in vitro experiments, and its capacity to facilitate tumor growth was also validated in in vivo studies. Results The up-regulation of UBE2L3 expression was observed in GC, and its high expression was found to be significantly associated with the degree of differentiation (χ2 = 6.153, P = 0.0131), TNM stage (χ2 = 6.216, P = 0.0447), and poor overall survival. In vitro, UBE2L3 has been shown to enhance functions in GC cell lines, such as promoting proliferation and invasion, and inhibiting apoptosis. In vivo experiments have validated the role of UBE2L3 in promoting tumor growth. Conclusions The findings of our study demonstrate the significant involvement of UBE2L3 in the pathogenesis and advancement of gastric cancer, suggesting its potential as a therapeutic target.

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Assessment of genetic polymorphisms within nuclear factor-κB signaling pathway genes in rheumatoid arthritis: Evidence for replication and genetic interaction

Cited by 7 publications

References 54 publications

Cytokine and chemokine gene expression in patients with clinically suspect arthralgia; a longitudinal study during progression to inflammatory arthritis or non-progression

Cytokine and chemokine gene expression in patients with clinically suspect arthralgia; a longitudinal study during progression to inflammatory arthritis or non-progression

Associations between <b><i>TNFAIP3</i></b> Polymorphisms and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis Update with Trial Sequential Analysis

UBE2L3 expression in human gastric cancer and its clinical significance

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