The effect of the Taq1A variant in the dopamine D₂ receptor gene and common CYP2D6 alleles on prolactin levels in risperidone-treated boys

Pharmacogenet Genomics. 2013 Sep;23(9):487-93. doi: 10.1097/FPC.0b013e3283647c33.

Abstract

Objective: To investigate the effect of the Taq1A variant in the Dopamine D2 receptor gene (DRD2) and common functional genetic variants in the cytochrome P450 2D6 gene (CYP2D6) on prolactin levels in risperidone-treated boys with autism spectrum disorders and disruptive behavior disorders.

Methods: Forty-seven physically healthy 10-year-old to 19-year-old boys with autism spectrum disorders and/or disruptive behavior disorders, chronically treated (mean 52 months, range 16-126 months) with an antipsychotic, were recruited into this observational study. Prolactin levels, hyperprolactinemia, risperidone levels, and 9-hydroxyrisperidone levels were assessed and the participants were genotyped for common CYP2D6 polymorphisms and the Taq1A allele of the dopamine D2 receptor gene. Group differences were tested using Student's t-test, χ², and logistic regression analysis.

Results: Prolactin levels were associated positively and significantly with risperidone levels (P=0.05), 9-hydroxyrisperidone levels (P≤0.0001), and with the oral risperidone dose in milligrams per kilogram (P≤0.0001). Furthermore, multiple regression analysis showed no correlations between prolactin level and the presence of at least one Taq1A A1 allele of the DRD2 gene (P=0.12).

Conclusion: Although CYP2D6 might have an effect, the presence of at least one Taq1A A1 allele of the D2DR gene did not contribute toward susceptibility to risperidone-induced hyperprolactinemia, and as a result, toward prolactin-related adverse events such as amenorrhea, galactorrhea, and sexual dysfunctioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Attention Deficit and Disruptive Behavior Disorders / drug therapy
  • Attention Deficit and Disruptive Behavior Disorders / psychology
  • Child
  • Child Development Disorders, Pervasive / drug therapy
  • Child Development Disorders, Pervasive / psychology
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Drug Administration Schedule
  • Genetic Variation
  • Humans
  • Hyperprolactinemia / chemically induced
  • Isoxazoles / metabolism
  • Isoxazoles / therapeutic use
  • Male
  • Paliperidone Palmitate
  • Polymorphism, Genetic*
  • Prolactin / blood*
  • Pyrimidines / metabolism
  • Pyrimidines / therapeutic use
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D2 / metabolism
  • Risperidone / administration & dosage
  • Risperidone / adverse effects*
  • Risperidone / therapeutic use
  • Young Adult

Substances

  • Antipsychotic Agents
  • DRD2 protein, human
  • Isoxazoles
  • Pyrimidines
  • Receptors, Dopamine D2
  • Prolactin
  • Cytochrome P-450 CYP2D6
  • Risperidone
  • Paliperidone Palmitate