title: Risperidone-associated adverse drug reactions and CYP2D6 polymorphisms in a South African cohort.
abstract: BACKGROUND
  Contradictory information exists regarding the influence of CYP2D6 polymorphisms on adverse drug reactions (ADRs) (extrapyramidal symptoms (EPS) and weight gain) related to risperidone treatment. This prompted us to evaluate the influence of CYP2D6 genetic variation in a cohort of South African patients who presented with marked movement disorders and/or weight gain while on risperidone treatment.
  
  
  METHODS
  Patients who were experiencing marked risperidone ADRs were recruited from Weskoppies Public Psychiatric Hospital. As poor or intermediate metabolism was expected, comprehensive CYP2D6 sequence variations were evaluated using XL-PCR + Sequencing.
  
  
  RESULTS
  No statistically significant association was found between CYP2D6 poor metabolism and risperidone ADRs. An inverse relationship between EPS and weight gain was however identified. A novel CYP2D6 allele was identified which is unlikely to affect metabolism based on in silico evaluation.
  
  
  CONCLUSIONS
  CYP2D6 variation appeared not to be a good pharmacogenetic marker for predicting risperidone-related ADRs in this naturalistic South African cohort. Evaluation of a larger cohort would be needed to confirm these observations, including an examination of the role of potential intermediaries between the hypothesised genetic and clinical phenotypes.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Pretoria, South Africa; Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, South Africa.
authors.forename: Tyren M
authors.initials: TM
authors.lastname: Dodgen
authors.affiliation: Department of Immunology, School of Medicine, University of Pretoria, South Africa.
authors.forename: Arinda
authors.initials: A
authors.lastname: Eloff
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pretoria, South Africa.
authors.forename: Connie
authors.initials: C
authors.lastname: Mataboge
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pretoria, South Africa.
authors.forename: Louw J L
authors.initials: LJ
authors.lastname: Roos
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pretoria, South Africa.
authors.forename: Werdie C W
authors.initials: WC
authors.lastname: van Staden
authors.affiliation: Department of Immunology, School of Medicine, University of Pretoria, South Africa; Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, South Africa; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
keywords: CYP2D6; Extrapyramidal symptoms; Risperidone; Weight gain