Associations between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis, and betweenMIFgene polymorphisms and disease susceptibility: a meta-analysis

Abstract Aim To systematically review evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis (RA), and the association between MIF gene polymorphisms and RA susceptibility. Design We performed a meta-analysis on data of serum/plasma MIF levels in patients with RA and in controls, and on associations between the MIF−173 C/G and −794CATT5-8 polymorphisms and RA susceptibility. Patients Twelve studies, comprising a total of 362 RA cases and 531 controls evaluated for MIF levels, and 2367 RA cases and 2395 controls evaluated for MIF polymorphisms, were included. Results MIF levels were significantly higher in the RA group than in the control group (standardised mean difference (95% CI) 0.923 (0.766 to 1.080), p<0.001). Stratification by ethnicity revealed significantly higher MIF levels in the RA group in Caucasian, Asian and Latin American populations. MIF levels were significantly higher in patients with RA, regardless of adjustment, sample size or data type evaluated. RA was identified to be significantly associated with the MIF−173 C allele (OR (95% CI) 1.271 (1.141 to 1.416), p<0.001), as well as with the −794CATT7 allele (OR (95% CI) 1.229 (1.084 to 1.415), p=0.002) and the −794CATT7-MIF-173C haplotype RA (OR (95% CI) 1.433 (1.138 to 1.805), p=0.002). Conclusions Our meta-analyses revealed significantly higher circulating MIF levels in patients with RA, and found evidence of associations between the MIF−173 C/G and −794CATT5-8 polymorphisms and RA susceptibility.