Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis

Yu Fu,Qing Lin,Zhi-Rong Zhang

doi:10.1186/s42358-021-00215-2

Abstract

ObjectiveTo more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility, we performed a meta-analysis on the association of the following single nucleotide polymorphisms (SNPs) of TNFSF4 with SLE: rs1234315, rs844648, rs2205960, rs704840, rs844644, rs10489265.MethodsA literature-based search was conducted using PubMed, MEDLINE, Embase, Web of Science databases, and Cochrane Library databases to identify all relevant studies. And the association of TNFSF4 gene polymorphisms and SLE susceptibility was evaluated by pooled odds ratio (OR) with 95% confidence interval (CI).ResultsThe meta-analysis produced overall OR of 1.42 (95% CI 1.36–1.49, P < 0.00001), 1.41 (95% CI 1.36–1.46, P < 0.00001) and 1.34 (95% CI 1.26–1.42, P < 0.00001) for the rs2205960, rs1234315 and rs704840 polymorphisms respectively, confirming these three SNPs confer a significant risk for the development of SLE. On the other hand, the meta-analysis produced overall OR of 0.92 (95% CI 0.70–1.21, P = 0.54) for the rs844644 polymorphism, suggesting no significant association. And no association was also found between either rs844648 1.11 (OR 1.11, 95% CI 0.86–1.43, P = 0.41) or rs10489265 (OR 1.17, 95% CI 0.94–1.47, P = 0.17) polymorphism with SLE susceptibility, respectively.ConclusionsOur meta-analysis demonstrated that the TNFSF4 rs2205960, rs1234315 and rs844840 SNPs was significantly associated with an increased risk of SLE.

Highlights

systemic lupus erythematosus (SLE) is a chronic multisystem complex autoimmune disorder, which is characterized by pathogenic humoral and cellular immunity to self-antigen [1]
As one of susceptibility genes for SLE involved in NF-κB signaling pathway, many studies have examined the association between TNFSF4 gene polymorphisms and the risk of SLE [7,8,9,10]
All SLE patients met the diagnostic criteria of the American College of Rheumatology and Newcastle–Ottawa Quality Assessment Scale (NOS) Scores were 6–8

Summary

Introduction

SLE is a chronic multisystem complex autoimmune disorder, which is characterized by pathogenic humoral and cellular immunity to self-antigen [1]. Great efforts have been made to identify the genes and genomic regions of SLE susceptibility through genetic association studies, especially genome-wide association studies (GWAS). Numerous susceptibility genes of SLE have been widely addressed, including HLA class II haplotypes, STAT4, MHC-I, NCF2, FCGR2B, BLK, IRF5/TNPO3, TNFAIP3, and TNFSF4 [3]. OX40-OX40L interaction promotes the survive and expansion of CD8 + T cells and the recall response of CD8 + memory T cell in vivo [12]. OX40-OX40L blockade in vivo may ameliorate autoimmunity by preventing migration and proliferation of T cells, affecting T cell polarization, altering cytokine production [9, 12]

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Conclusion