Influence of beta-Defensin-2, -3 und -4 gene copy number variations on gene transcription and protein expression, and their impact on infectious complications in trauma patients

• Applicant: Dr. Malte Book
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2003 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5407425

Trauma patients on surgical intensive care units are at high risk of developing severe infections including shock and organ failure. The antimicrobial activity of Defensins against bacteria, fungi and coated virus as well as their chemotactic activity on dendritic- and T-cells (innate immunity) are essential parts in the immunologic defence lines against infection. Our own previous work indicated interindividual differences in inducibility of b2-Defensin which is the most effective human antimicrobial Defensin. Sequence analysis of the regulatory regions of the b2-Defensin gene detected 5 single nucleotide polymorphisms in the promoter region. The functional impact of these polymorphisms on transcriptional regulation of b2-Defensin will be investigated by reporter gene constructs in this project. Moreover, in cooperation with other projects in this research network the project on genetic predisposition for adverse outcomes from trauma will analyse the impact of these genomic variations on adverse outcomes. The aim is to investigate the association of these 5 promoter polymorphisms with incidence, severity and survival of infectious complications. In addition, cooperations within the trauma research network led by Prof. Schade will enable studies on defensin expression related to genotype.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1151: Immune and Metabolic Modulation Induced by Severe Tissue Trauma
• International Connection: Switzerland
• Participating Person: Professor Dr. Frank Stüber