No influence of CYP3A43 rs472660G> A on steady-state serum olanzapine concentrations in white psychiatric patients

Pharmacogenet Genomics. 2014 May;24(5):272-5. doi: 10.1097/FPC.0000000000000041.

Abstract

The potential involvement of CYP3A43 in systemic olanzapine (OLA) metabolism has been suggested by one reported association between the intronic polymorphism CYP3A43 rs472660G>A and OLA clearance in 235 White and African-American patients. Trough plasma OLA concentrations in AA carriers were predicted on average 48% lower than in GG carriers. In the current study, we evaluated this finding by genotyping 374 White psychiatric patients on long-term OLA treatment. No significant difference in dose-adjusted trough serum OLA concentrations was observed between the seven AA carriers identified and the other two genotypes, without (P=0.6) or with (P=0.23) adjustment for additional covariates previously known to influence systemic OLA exposure. Because of the low prevalence of the rs472660 AA genotype in White populations (2%), larger study cohorts are needed for future association confirmation. Overall, CYP3A43 rs472660 is not likely to be a major contributor towards variability in systemic OLA exposure among White patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / blood
  • Bipolar Disorder / blood
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / genetics*
  • Black or African American / genetics
  • Female
  • Genotype
  • Humans
  • Male
  • Olanzapine
  • Polymorphism, Genetic
  • Schizophrenia / blood
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • White People / genetics

Substances

  • Benzodiazepines
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A43 protein, human
  • Olanzapine