Replication of SULT4A1-1 as a pharmacogenetic marker of olanzapine response and evidence of lower weight gain in the high response group

Pharmacogenomics. 2014 May;15(7):933-9. doi: 10.2217/pgs.14.54.

Abstract

Aim: Antipsychotic efficacy biomarkers have the potential to improve outcomes in psychotic patients. This study examined the effect of SULT4A1-1 haplotype status (rs2285162 [A]-rs2285167 [G]) on olanzapine response.

Patients & methods: We evaluated 87 olanzapine treated subjects from Phases 1, 1B and 2 of the CATIE trial for the impact of SULT4A1-1 status on change in Positive and Negative Syndrome Scale (PANSS) total score using two models of response. We also examined weight change.

Results: SULT4A1-1-positive status correlated with superior olanzapine response in Phase 1 (p = 0.004 for model 1 and p = 0.001 for model 2) and Phases 1B/2 (p = 0.05 for model 1 and p = 0.007 for model 2). SULT4A1-1-positive subjects gained significantly less weight per month on olanzapine, 0.15 lbs, than did SULT4A1-1-negative subjects, 2.27 lbs (p = 0.04).

Conclusion: This study provides a second replication of superior olanzapine response in SULT4A1-1-positive subjects compared with SULT4A1-1-negative subjects. SULT4A1-1-positive subjects treated with olanzapine also gained less weight than SULT4A1-1-negative subjects.

Keywords: CATIE trial; antipsychotic response; biomarker; weight gain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / adverse effects
  • Clinical Trials as Topic
  • Female
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Pharmacogenetics*
  • Sulfotransferases / genetics*
  • Weight Gain / drug effects
  • Weight Gain / genetics*

Substances

  • Antipsychotic Agents
  • Benzodiazepines
  • SULT4A1 protein, human
  • Sulfotransferases
  • Olanzapine