title: The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency.
abstract: OBJECTIVE
  Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals.
  
  
  METHODS
  Sixty-seven cocaine-dependent patients were stabilized on methadone for 2 weeks and then randomized into disulfiram (250 mg/day, N = 32) and placebo groups (N = 35) for 10 weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10 weeks of the study (N = 56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure.
  
  
  RESULTS
  The CT or TT MTHFR genotype group (N = 32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p = 0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N = 24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81-69% (p = 0.007).
  
  
  CONCLUSIONS
  This study indicates that a patient's MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence.
  
  
  BACKGROUND
  Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630.
authors: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine and Michael E. DeBakey V. A. Medical Center Houston, TX, USA.
authors: Catherine J
authors: CJ
authors: Spellicy
authors: Thomas R
authors: TR
authors: Kosten
authors: Sara C
authors: SC
authors: Hamon
authors: Mark J
authors: MJ
authors: Harding
authors: David A
authors: DA
authors: Nielsen
keywords: cocaine; dependence; disulfiram; genes; polymorphism; treatment