title: A pharmacogenetic exploration of vigabatrin-induced visual field constriction.
abstract: BACKGROUND
  Use of the antiepileptic drug (AED) vigabatrin is severely limited by irreversible visual field constriction, an adverse reaction to the drug reported in approximately 40% of patients. Given the evidence suggesting an idiosyncratic drug response, we set out to detect genetic variation of strong, clinically relevant effect that might guide clinicians in the safe, controlled prescribing of this otherwise usefuldrug.
  
  
  METHODS
  Patients with a history of at least 1-year exposure to vigabatrin were enrolled at two independent referral centers. Using Goldmann perimetry, visual fields and the extent of constriction were calculated for each patient. We examined the correlation between the extent of vigabatrin induced visual field constriction and genetic variation across six candidate genes (SLC6A1, SLC6A13, SCL6A11, ABAT, GABRR1 and GABRR2). We availed of HapMap data and used a tagging SNP technique in an effort to efficiently capture all common variation within these genes. We attempted to replicate any positive associations before drawing conclusions from our results.
  
  
  RESULTS
  The degree of visual field constriction correlated with three SNPs and one haplotype in a cohort of 73 patients. However we were unable to replicate these findings in a second independent cohort consisting of 58 patients, suggesting the initial results were possibly false positives, or variants of weak effect.
  
  
  CONCLUSIONS
  Common variants of strong, clinically relevant effect do not appear to reside in the candidate genes studied here. This does not rule out the presence of genetic variants of weak effect in these genes, nor of variants of strong effect in other genes.
authors: Department of Clinical Neurological Sciences, Royal College of Surgeons, Division of Neurology, Beaumont Hospital, Dublin, Ireland.
authors: Peter
authors: P
authors: Kinirons
authors: Gianpiero L
authors: GL
authors: Cavalleri
authors: Rinki
authors: R
authors: Singh
authors: Amre
authors: A
authors: Shahwan
authors: James F
authors: JF
authors: Acheson
authors: Nicholas W
authors: NW
authors: Wood
authors: David B
authors: DB
authors: Goldstein
authors: Sanjay M
authors: SM
authors: Sisodiya
authors: Colin P
authors: CP
authors: Doherty
authors: Norman
authors: N
authors: Delanty