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

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.