Molecular genetics of adverse drug reactions: from candidate genes to genome wide association studies

Research summary

Adverse drug reactions (ADR's) are a common cause of drug-related morbidity and may account for about 6.5% of all hospital admissions. A meta-analysis of studies performed in the USA has shown that ADRs may be the fourth commonest cause of death. ADRs are also a significant impediment to drug development, and a significant cause of drug withdrawal. The purpose of this research is to (a) identify patients with different types of adverse drug reactions; (b) using DNA obtained from blood or Saliva samples from these patients, identify genetic factors which predispose to adverse reactions. The net effect of our research will be the development of genetic tests which can help in predicting individual susceptibility to adverse reactions prior to the medication's administration. Patients with a pre-disposition to reacting adversely can be prescribed alternative medication of monitored more closely during their treatment. This will reduce the harm for patients and save valuable resources for the NHS. We aim to recruit 250 cases for each reaction for a period of eight years throughout multiple sites in the UK. Specific adverse drug reactions we are looking at include: - Statin induced myotoxicity, characterised by high CK - Severe hypersensitivity reactions including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis - Anaphylaxis induced by NMBA anaesthetics - ACE inhibitor or ARB induced angioedema - Taxane hypersensitivity - Chemotherapy induced peripheral neuropathy - Bleomycin induced lung toxicity - Clozipine induced agranulocytosis or neutropenia - Bisphosphonate-related osteonecrosis of the jaw - Tenofovir associated renal injury - Serious bleeds induced by warfarin or other anticoagulants Arms for Dihydropyrimidine Dehydrogenase (DPYD) Glaucoma Anthracycline of Induced Cardiotoxicity (ACT) are now open on the study.

Principal Investigator

Dr Siraj A Misbah

Contact us

Email: crndirectdeliveryteam@ouh.nhs.uk

IRAS number

7086