Macrophage migration inhibitory factor (MIF) promoter polymorphism in inflammatory disease

US9139877B2 · kind B2 · utility

Assignee

• Baxalta Incorporated · CH

Inventors

• John Baugh · Greystones, IE
• Richard J. Bucala · New York, US
• Smita Chitnis · San Diego, US
• Seamus C. Donnelly · Dublin, IE
• Peter K. Gregersen · Larchmont, US
• Joanita Monteiro · Philadelphia, US

Key dates

• Filing date: Dec 6, 2012
• Grant date: Sep 22, 2015
• Expiry date: Dec 6, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q2600/156
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Describe herein is a novel CATT-tetranucleotide repeat polymorphism at position −817 of the human Mif that functionally affects the activity of the Macrophage Inhibitory Factor (MIF) promoter in gene reporter assays. Four genotypes are described which comprise 5, 6, 7, or 8-CATT repeat units. Of these, 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. Methods, compositions and apparatus for detecting this CATT-tetranucleotide repeat polymorphism at position −817 of the human Mif gene, and for using same for assessing predisposition to severe inflammatory disease, are also disclosed.