Pharmacogenetic data for inflammatory bowel disease
Inflammatory bowel disease is a condition that causes vomiting, diarrhoea, weight loss and is sometimes associated with other atopic diseases like arthritis and asthma. Although the disease can be triggered by factors associated with modern lifestyle, gene complexes associated with susceptibility have been found on chromosomes 6, 12 and 16. Pharmacological treatment with glucocorticoids is successful, but only in about two out of three cases. Anti-tumour necrosis factor (TNF) alpha monoclonal antibodies can be administered to refractory patients not responding to steroid treatment but are limited in success to the same extent. To find the biomolecular basis for failure of these therapies provided the catalyst for the investigation into new pharmacogenetic therapies. Two groups of refractory patients were studied by project partners at the University Hospital of Schleswig-Holstein. Altogether, some 570 patients constituted the largest and most diverse study group to date. The two cohorts of patients were given the infliximab anti-TNF monoclonal antibody. Previously identified single nucleotide polymorphisms (SNPs) in novel inflammation genes were scrutinised. Samples of DNA were first amplified using the semi-automated polymerase chain reaction and then subjected to a Taqman drug response analysis. Data analysis used case-control statistics and multiple regression models. These methods ensured the identification of statistically independent predictors of response to drugs. Moreover, the scientists took corroborative samples from other trials and re-tested the results to eradicate statistical errors known as false positives. Outcomes of this comprehensive and thorough piece of research were that variants of the tumour necrosis factor system and the NOD2 gene, which is linked to inflammatory bowel disease, were analysed. Future research was planned involving the combined effects of different gene variants in both pathways with a view to clinical trials using the new markers. Genetic profiles of patients to indicate appropriate drug therapy constitutes a major step forward in the treatment of inflammatory bowel disease.
