Renner, Pascal, Roger, Thierry, Bochud, Pierre-Yves, Sprong, Tom, Sweep, Fred C.G.J., Bochud, Murielle, Faust, Saul N., Haralambous, Elene, Betts, Helen, Chanson, Anne-Laure, Reumond, Marlies Knaup, Mermel, Elliott, Erard, Veronique, van Deuren, Marcel, Read, Robert C., Levin, Michael and Calandra, Thierry (2012) A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease. The FASEB Journal, 26 (2), 907-916. (doi:10.1096/fj.11-195065). (PMID:21990375)
Abstract
Macrophage migration inhibitory factor (MIF) is an abundantly expressed proinflammatory cytokine playing a critical role in innate immunity and sepsis and other inflammatory diseases. We examined whether functional MIF gene polymorphisms (-794 CATT(5-8) microsatellite and -173 G/C SNP) were associated with the occurrence and outcome of meningococcal disease in children. The CATT(5) allele was associated with the probability of death predicted by the Pediatric Index of Mortality 2 (P=0.001), which increased in correlation with the CATT(5) copy number (P=0.04). The CATT(5) allele, but not the -173 G/C alleles, was also associated with the actual mortality from meningoccal sepsis [OR 2.72 (1.2-6.4), P=0.02]. A family-based association test (i.e., transmission disequilibrium test) performed in 240 trios with 1 afflicted offspring indicated that CATT(5) was a protective allele (P=0.02) for the occurrence of meningococcal disease. At baseline and after stimulation with Neisseria meningitidis in THP-1 monocytic cells or in a whole-blood assay, CATT(5) was found to be a low-expression MIF allele (P=0.005 and P=0.04 for transcriptional activity; P=0.09 and P=0.09 for MIF production). Taken together, these data suggest that polymorphisms of the MIF gene affecting MIF expression are associated with the occurrence, severity, and outcome of meningococcal disease in children.-Renner, P., Roger, T., Bochud, P.-Y., Sprong, T., Sweep, F. C. G. J., Bochud, M., Faust, S. N., Haralambous, E., Betts, H., Chanson, A.-L., Reymond, M. K., Mermel, E., Erard, V., van Deuren, M., Read, R. C., Levin, M., Calandra, T. A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease.
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