Association of IRF5 rs2004640 polymorphism and systemic lupus erythematosus: A meta‐analysis

Abstract

Background This study aimed to discuss the relationship between interferon regulatory factor (IRF)5 gene rs2004640 T/G polymorphism and systemic lupus erythematosus (SLE) susceptibility. Methods A meta‐analysis was calculated on the association between rs2004640 polymorphism and SLE by allelic contrast (T vs G), additive model (TT vs GG), recessive model (TT vs TG + GG) and dominant model (TT + TG vs GG). Results A total of 28 comparisons were identified, including 11 228 SLE cases and 14 374 controls. Meta‐analysis revealed a significant association between allele T and SLE in overall populations (odds ratio [OR] = 1.393, 95% CI: 1.276‐1.522, P < 0.001). Stratification by ethnicity indicated strong associations between T allele and SLE in Asians, Europeans and Latin Americans (OR = 1.256, 95% CI: 1.073‐1.469, P = 0.004; OR = 1.338, 95% CI: 1.080‐1.659, P = 0.008; OR = 1.853, 95% CI: 1.488‐2.308, P < 0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR = 1.999, 95% CI: 1.442‐2.771, P < 0.001; OR = 1.544, 95% CI: 1.009‐2.362, P < 0.045). In addition, we found significant associations between the dominant model and SLE in all populations and Asians (OR = 1.521, 95% CI: 1.257‐1.841, P < 0.001; OR = 1.270, 95% CI: 1.136‐1.421, P < 0.001). A marginal association was detected between the recessive mode and SLE in overall subjects (OR = 1.480, 95% CI: 1.022‐2.144, P = 0.038). Conclusion The current study suggested that individuals carrying rs2004640 T allele correlated with a high risk of SLE, and the IRF5 rs2004640 polymorphism was associated with SLE susceptibility.

IRF5‐TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study

“…18 In addition, the rs2004640 TT genotype has been previously associated with higher levels of IRF5 mRNA expression, likely leading to excessive IFN-I production-enhancing immune responses. 11 The rs10954213 SNP is in a conserved 3' untranslated region (3' UTR) of the IRF5 gene. The rs10954213 A variant has previously shown a strong association with IRF5 expression, even higher than other IRF5 variants.…”

“…The rs2004640 T allele creates a donor splice site in an alternate exon 1 of the IRF5 gene (exon 1B), allowing the expression of several unique IRF5 isoforms 18 . In addition, the rs2004640 TT genotype has been previously associated with higher levels of IRF5 mRNA expression, likely leading to excessive IFN‐I production‐enhancing immune responses 11 . The rs10954213 SNP is in a conserved 3’ untranslated region (3’ UTR) of the IRF5 gene.…”

“…Specifically, rs2004640, rs10954213, and rs2280714 SNPs have been associated with increased expression of IRF5 and excessive production of IFN-I. [11][12][13] Previous studies have shown that the downregulation of TNPO3 with siRNAs reduces nuclear import, HIV-1 integration, and infectivity. [14][15][16] However, there is no previous information about the effect of IRF5-TNPO3 SNPs on TNPO3 expression.…”

“…The IRF5–TNPO3 SNPs have previously been related to the modulation of the immune system. Specifically, rs2004640, rs10954213, and rs2280714 SNPs have been associated with increased expression of IRF5 and excessive production of IFN‐I 11–13 . Previous studies have shown that the downregulation of TNPO3 with siRNAs reduces nuclear import, HIV‐1 integration, and infectivity 14–16 .…”

IFN-γ, should not be ignored in SLE

“…A SNP of STAT4 (rs7574865) ( 33 ) was found to be associated with SLE in the IFN-STAT signaling pathway. In addition, many SNPs of interferon regulated factors (IRFs) have also been found to be associated with the risk of developing SLE, including IRF3 rs2304206 ( 34 ), IRF5 rs200464 ( 35 ), IRF7 rs1131665 ( 36 ), IRF8 rs11644034 and rs2280381 ( 37 ) polymorphism. More important, epigenetic regulation is an important mechanism of transcriptional activation in SLE pathogenesis.…”