Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.

Abstract

OBJECTIVES The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population. METHODS: A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay. RESULTS: The MIF -173 SNP showed association with SSc [P\u2009=\u20090.04, odds ratio (OR)\u2009=\u20091.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P\u2009=\u20095.30E-03, OR\u2009=\u20091.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P\u2009=\u20090.04, OR\u2009=\u20090.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P\u2009=\u20090.005, OR\u2009=\u20090.83, 95% CI 0.73, 0.94)]. CONCLUSION: Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker