title: The effect of the Taq1A variant in the dopamine D₂ receptor gene and common CYP2D6 alleles on prolactin levels in risperidone-treated boys.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: GGZ Central Psychiatric Centre, Amersfoort, The Netherlands. y.roke@ggzcentraal.nl
authors.forename: Yvette
authors.initials: Y
authors.lastname: Roke
authors.forename: Peter N
authors.initials: PN
authors.lastname: van Harten
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Tessel E
authors.initials: TE
authors.lastname: Galesloot
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: Boot
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
mesh_terms: D000293:Adolescent; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000188:drug therapy / Q000523:psychology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy / Q000523:psychology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D004334:Drug Administration Schedule; D014644:Genetic Variation; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced; D007555:Isoxazoles / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D000068882:Paliperidone Palmitate; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000097:blood*; D011743:Pyrimidines / Q000378:metabolism / Q000627:therapeutic use; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C581293:DRD2 protein, human; D007555:Isoxazoles; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D011388:Prolactin; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate