Associations between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis, and between <i>MIF</i> gene polymorphisms and disease susceptibility: a meta-analysis.

Abstract

To systematically review evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis (RA), and the association between <i>MIF</i> gene polymorphisms and RA susceptibility. We performed a meta-analysis on data of serum/plasma MIF levels in patients with RA and in controls, and on associations between the <i>MIF</i>-173 C/G and -794CATT_5-8 polymorphisms and RA susceptibility. 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 <i>MIF</i> polymorphisms, were included. 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 <i>MIF</i>-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-<i>MIF</i>-173C haplotype RA (OR (95% CI) 1.433 (1.138 to 1.805), p=0.002). Our meta-analyses revealed significantly higher circulating MIF levels in patients with RA, and found evidence of associations between the <i>MIF</i>-173 C/G and -794CATT_5-8 polymorphisms and RA susceptibility.