Single nucleotide polymorphism rs5029937 in TNFAIP3 gene is correlated with risk of rheumatoid arthritis

Pakzad, Bahram; Yousefisadr, Farzaneh; Karimzadeh, Hadi; Mousavi, Maryam; Noormohamadi, Elham; Salehi, Roya

doi:10.47176/mjiri.35.42

Cited by 2 publications

(3 citation statements)

References 33 publications

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“…The NLRP3 rs1539019 polymorphism is an intronic variation whose function is still not entirely understood. However, several studies have reported that intronic polymorphisms may be associated with susceptibility/resistance to several diseases, such as rheumatoid arthritis [ 56 ], type II diabetes [ 57 ], and coronary artery disease [ 58 ]. One explanation for this is that many transcription factors bind to intronic sites that may play a role in regulating gene expression.…”

Section: Discussionmentioning

confidence: 99%

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

Sá

Neira-Goulart

Ribeiro-Alves

et al. 2022

BioMed Research International

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COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease ( WHO < 6 ; n = 76 ), and group 2 included patients with severe/critical COVID-19 ( WHO ≥ 6 ; n = 357 ). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic – National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype ( OR adj = 0.36 ; P = 0.032 ), allele A ( OR adj = 0.93 ; P = 0.010 ), or carrier-A ( OR adj = 0.45 ; P = 0.027 ) in the NLRP3 rs1539019 polymorphism; A/T genotype ( OR adj = 0.5 ; P = 0.045 ), allele T ( OR adj = 0.93 ; P = 0.018 ), or carrier-T ( OR adj = 0.48 ; P = 0.029 ) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C ( OR adj = 0.11 ; P = 0.018 ), A-C-G-C-G ( OR adj = 0.23 ; P = 0.003 ), C-C-G-C-C ( OR adj = 0.37 ; P = 0.021 ), and C-T-G-A-C ( OR adj = 0.04 ; P = 0.0473 ) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

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Section: Discussionmentioning

confidence: 99%

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

Sá

Neira-Goulart

Ribeiro-Alves

et al. 2022

BioMed Research International

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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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Single nucleotide polymorphism rs5029937 in TNFAIP3 gene is correlated with risk of rheumatoid arthritis

Cited by 2 publications

References 33 publications

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

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

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