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ABSTRACT The macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine and regulates the anti-inflammator effects of glucocorticoids. An important role for MIF

within the cytokine cascade is to act in concert with endogenous glucocorticoids to control the set-point and magnitude of the inflammatory response. Elevated expression of MIF in the

circulation and in the synovial joint has been documented in rheumatoid arthritis. MIF also has been linked to the development of joint damage and disease pathology in experimental animal

models. We describe herein a novel CATT-tetranucleotide repeat polymorphism at position −794 of the human Mif gene and show that it functionally affects the activity of the MIF promoter in

gene reporter assays. We describe four genotypes which comprise 5, 6, 7, or 8-CATT repeat units and show that the 5-CATT allele has the lowest level of basal and stimulated MIF promoter

activity _in vitro_. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients. Access through your

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notes * J A Baugh and S Chitnis: These authors contributed equally to this work; SC originally identified the MIF-CATT polymorphism and performed population studies. AUTHORS AND AFFILIATIONS

* Laboratory of Medical Biochemistry, The Picower Institute for Medical Research, 350 Community Drive, Manhasset, 11030, NY, USA J A Baugh, S C Donnelly, X Lin & R Bucala * Center for

Genomics and Human Genetics, North Shore Long Island Jewish Research Institute, 350 Community Drive, Manhasset, 11030, NY, USA S Chitnis, J Monteiro & P K Gregersen * Department Medicine

& Therapeutics, Conway Institute, St. Vincent’s Hospital, Elm Park, Dublin, 4, Ireland S C Donnelly & B J Plant * Arthritis Research Center, Wichita, Kansas, 67214, MO, USA F Wolfe

Authors * J A Baugh View author publications You can also search for this author inPubMed Google Scholar * S Chitnis View author publications You can also search for this author inPubMed 

Google Scholar * S C Donnelly View author publications You can also search for this author inPubMed Google Scholar * J Monteiro View author publications You can also search for this author

inPubMed Google Scholar * X Lin View author publications You can also search for this author inPubMed Google Scholar * B J Plant View author publications You can also search for this author

inPubMed Google Scholar * F Wolfe View author publications You can also search for this author inPubMed Google Scholar * P K Gregersen View author publications You can also search for this

author inPubMed Google Scholar * R Bucala View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to P K Gregersen or R

Bucala. ADDITIONAL INFORMATION The authors would like to acknowledge support form the NIH (RB – 1R01-AI35931, 1R01-AI42310; PKG – RO1-AR44222), The Wellcome Trust, and The Picower Institute

for Medical Research. We also thank Ms Nina Kohn for expert assistance with biostatistical analysis. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE

Baugh, J., Chitnis, S., Donnelly, S. _et al._ A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid

arthritis. _Genes Immun_ 3, 170–176 (2002). https://doi.org/10.1038/sj.gene.6363867 Download citation * Received: 02 January 2002 * Revised: 06 February 2002 * Accepted: 06 February 2002 *

Published: 21 May 2002 * Issue Date: 01 May 2002 * DOI: https://doi.org/10.1038/sj.gene.6363867 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content:

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macrophage migration inhibitory factor * gene-polymorphism * rheumatoid arthritis