Abstract
IntroductionAdult-onset still's disease (AOSD) is a rare systemic inflammatory disorder in which abnormalities in inflammatory cytokines production appear to play a pathophysiological role. Our previous work has reported increased expression of macrophage migration inhibitory factor (MIF) and revealed its correlation with disease severity and activity in AOSD. A -173 G/C single nucleotide polymorphism (SNP) (rs755622) and a -794 CATT5-8 repeat (rs5844572) in the MIF promoter have been reported. In this study, we sought to explore the relationship between functional MIF promoter polymorphisms and MIF expression in AOSD.Methods100 patients and 200 controls were recruited in the study. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the -173 G/C SNP (rs755622) and PCR-based size discrimination assay was applied to detect the -794 CATT5-8 repeat (rs5844572) in the MIF promoter. Plasma MIF levels were measured by ELISA. MIF mRNA levels were quantified by real-time reverse transcription (RT)-PCR. Bisulfate genomic sequencing was employed to evaluate DNA methylation status within the MIF promoter.ResultsWe identified that the frequencies of MIF -794 CATT5 (P = 0.001) allele and the expression of MIF (P <0.001) were increased in patients compared to healthy controls. Plasma levels of MIF in patients with CC genotype were higher than those of patients with GC or GG genotypes (P = 0.05). In patients with established AOSD, a higher frequency of -794 CATT7 containing MIF genotypes was observed in those with liver dysfunction (P = 0.009). Haplotype analysis revealed a higher representation of the MIF haplotype defined by -173*C/-794 CATT5 (C5) in AOSD patients (P = 0.001).ConclusionFunctional promoter polymorphisms in the MIF gene influence plasma MIF levels in AOSD and may contribute to disease susceptibility or clinical presentation of AOSD.
Highlights
Adult-onset still’s disease (AOSD) is a rare systemic inflammatory disorder in which abnormalities in inflammatory cytokines production appear to play a pathophysiological role
We identified that the frequencies of migration inhibitory factor (MIF) -794 CATT5 (P = 0.001) allele and the expression of MIF (P < 0.001) were increased in patients compared to healthy controls
Our previous work has revealed an association of serum MIF expression with disease activity and severity in AOSD [12], which was later confirmed by Becker and colleagues [13]
Summary
Adult-onset still’s disease (AOSD) is a rare systemic inflammatory disorder in which abnormalities in inflammatory cytokines production appear to play a pathophysiological role. Our previous work has reported increased expression of macrophage migration inhibitory factor (MIF) and revealed its correlation with disease severity and activity in AOSD. We sought to explore the relationship between functional MIF promoter polymorphisms and MIF expression in AOSD. Adult-onset still’s disease (AOSD) is a rare systemic inflammatory disorder characterized by spiking fevers, an evanescent salmon pink rash, arthritis, leucocytosis, and multiple organ involvement [1]. Our previous work has revealed an association of serum MIF expression with disease activity and severity in AOSD [12], which was later confirmed by Becker and colleagues [13]
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