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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) (<jats:italic>rs755622<\/jats:italic>) and a -794 CATT<jats:sub>5-8<\/jats:sub> repeat (<jats:italic>rs5844572<\/jats:italic>) in the <jats:italic>MIF<\/jats:italic> promoter have been reported. In this study, we sought to explore the relationship between functional <jats:italic>MIF<\/jats:italic> promoter polymorphisms and MIF expression in AOSD.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>100 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 (<jats:italic>rs755622<\/jats:italic>) and PCR-based size discrimination assay was applied to detect the -794 CATT<jats:sub>5-8<\/jats:sub> repeat (<jats:italic>rs5844572<\/jats:italic>) in the <jats:italic>MIF<\/jats:italic> 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 <jats:italic>MIF<\/jats:italic> promoter.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We identified that the frequencies of <jats:italic>MIF<\/jats:italic> -794 CATT<jats:sub>5<\/jats:sub> (<jats:italic>P<\/jats:italic> = 0.001) allele and the expression of MIF (<jats:italic>P<\/jats:italic> &lt;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 (<jats:italic>P<\/jats:italic> = 0.05). In patients with established AOSD, a higher frequency of -794 CATT<jats:sub>7<\/jats:sub> containing <jats:italic>MIF<\/jats:italic> genotypes was observed in those with liver dysfunction (<jats:italic>P<\/jats:italic> = 0.009). Haplotype analysis revealed a higher representation of the <jats:italic>MIF<\/jats:italic> haplotype defined by -173*C\/-794 CATT<jats:sub>5<\/jats:sub> (C5) in AOSD patients (<jats:italic>P<\/jats:italic> = 0.001).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Functional promoter polymorphisms in the <jats:italic>MIF<\/jats:italic> gene influence plasma MIF levels in AOSD and may contribute to disease susceptibility or clinical presentation of AOSD.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4239","type":"journal-article","created":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T17:02:03Z","timestamp":1369933323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["A genetic role for macrophage migration inhibitory factor (MIF) in adult-onset Still's disease"],"prefix":"10.1186","volume":"15","author":[{"given":"Fang-Fang","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Fang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Leng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Bucala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Le","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang-Jing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,10,17]]},"reference":[{"key":"3976_CR1","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1136\/ard.2005.042143","volume":"65","author":"P Efthimiou","year":"2006","unstructured":"Efthimiou P, Paik PK, Bielory L: Diagnosis and management of adult onset Still's disease. 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