Genetic association analysis of polymorphisms in four cytochrome P450 genes, the MDR1 gene and treatment-outcome in Xhosa schizophrenia patients
ENGLISH ABSTRACT: Rapidly expanding knowledge of the human genome allows new insight into the interaction between drugs and DNA. The heterogeneic nature of schizophrenia is known to cause different patients to display dissimilar drug responses, reflecting distinct genetic profiles. Resulting adverse side effects include tardive dyskinesia (TD), a movement disorder associated with the long-term use of antipsychotic drugs. The identification of a pharmacogenetic basis of TD may have significant clinical implications in the treatment of schizophrenia, allowing individualised prescription of antipsychotic drugs and eventual elimination of undesirable side effects. The current study focussed on a number of South African Xhosa schizophrenia patients, some of whom have been diagnosed with TD. The investigation sought to establish whether the underlying mechanism causing the disorder to manifest only in some individuals, might be attributed to differences in DNA sequences, i.e. genomic susceptibility. A number of candidate polymorphisms in the CYP and MDR1 genes were evaluated in three separate analyses. (The same approach was followed in each investigation, and only known polymorphisms were selected.) The incidences of the various variants were compared between TD and non-TD patients. In addition, potential predisposing factors, i.e. tobacco and cannabis smoking and anhedonia, were taken into consideration. These were analysed concurrently with DNA data and TD status.