GENOSEPT - Genetics of sepsis in Europe

EC contribution: : € 2.000.000
Duration: : 48 months
Starting date: : 01/01/2005
Funding scheme: : Specific Targeted Research Projectx
Keywords: : intensive care medicine, sepsis, mortality, epidemiology, genetic testing, genetic predisposition
Contract/Grant agreement number: : LSHB-CT-2004-512155
Project web-site: : www.genosept.eu

Background:

GenOSept is a STREP which uses a multidisciplinary fundamental genomics approach (gene expression, structural genomics and population genetics) to examine genetic predisposition to sepsis.

Sepsis (a life-threatening infection) is a major public health problem throughout Europe. In the USA, in 1995, it cost $17 billion to treat 751 000 patients with severe sepsis, of whom 28.6% died. The Centre for Disease Control suggests that sepsis-attributable mortality rates are rising. We hypothesise that susceptibility to expensive new treatments and fatal outcomes from severe sepsis are, in part, genetically determined.

The GenOSept project will test this hypothesis. The partners aimed to standardise protocols for genotyping, facilitate application of new knowledge in functional and structural genomics, harmonise high-throughput genotyping and quality control between major European centres, and contribute to reducing sepsis-related mortality in European healthcare.

Aim:

Genetic predisposition for the incidence and outcome of sepsis has been recognised and suggested as a possible powerful tool for future risk stratification and even as inclusion criteria for therapeutic trials. GenOSept also contains a module which links patterns of gene expression with patterns of genomic variation in corresponding genes.

Genomic variants may influence the individual phenotype including gene expression levels and patterns, as well as protein levels and protein structure. A possible result is that future intensive care physicians may have access to readily available genetic risk patterns including pharmacogenetics of their patients which not only allows for better risk stratification, but may also help tailor individual patient care and drug therapy.

The major milestones of GenOSept were:

consensus definitions and the setting up of an inclusion and exclusion criteria database;
collection of blood samples from about 2500 patients all over Europe;
blood genotyping and genetic testing;
identification of relevant candidate genes and their genomic variations;
genetic epidemiology study to be performed in European intensive care units (ICUs);
definition of a diagnostic SNP set.

Expected and obtained results:

The expected results of GenOSept are that, among others, it will:

contribute to unravelling the genetic predisposition of sepsis;
define novel candidate genes by gene expression studies;
include genes directing pathways of the host immune response to infection and inflammation, and of programmed cell death.

The novel genes identified by expression studies will add to a set of candidate genes used in a subsequent epidemiologic study which will:

standardise protocols for genotyping to facilitate application of new knowledge in functional and structural genomics;
harmonise standards for European high-throughput genotyping and quality control by coordinating major European genotyping centres;
deliver data on gender-related mortality and morbidity.

Potential applications:

The GenOSept findings will contribute to reducing sepsis-mortality and morbidity in European ICUs. The project will link fundamental genomics to sepsis, a major European public health issue. The application of gene expression studies and structural genome analysis detecting genomic variation will generate novel data on relevant genes as well as novel genomic variations involved in the genetic predisposition of incidence and outcome from sepsis. The evaluation and use of novel techniques, including the gene chip technology and the establishment of a European network of clinical and laboratory groups working in the field of critical care medicine, will strengthen European biotech industry.

Coordinator:

Prof. Julian Bion and Dr Nathalie Mathy
European Society of Intensive Care Medicine
Brussels, Belgium
Tel. 32 2 5590353
Fax 32 25270062
public@esicm.org