Sorted By Test Name - Mayo Medical Laboratories

DRD3O
60342
should be monitored closely for signs of tardive dyskinesia if a decision is made to treat with
antipsychotics. Testing may also be considered for individuals who will receive antipsychotic
medications, if they are first-degree relatives of patients who have developed tardive dyskinesia.
Assessing potential for effective treatment response with clozapine, olanzapine, and risperidone
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Lerer B, Segman RH, Fangerau H, et al: Pharmacogenetics of tardive
dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene
Ser9Gly polymorphism. Neuropsychopharmacology 2002;27:105-119 2. de Leon J, Susce MT, Pan RM,
et al: Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3
receptors and their association with tardive dyskinesia in severe mental illness. J Clin Psychopharmacol
2005;25:448-456 3. Scharfetter J, Chaudry HR, Hornik K, et al: Dopamine D3 receptor gene
polymorphism and response to clozapine in schizophrenic Pakistani patients. Eur Neuropsychopharmacol
1999;10(1):17-20 4. Lane HY, Hsu SK, Liu YC, et al: Dopamine D3 receptor Ser9Gly polymorphism and
risperidone response. J Clin Psychopharmacol 2005;25(1):6-11 5. Reynolds GP, Yao Z, Zhang X, et al:
Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms
separately associate with positive and negative symptom response. Eur Neuropsychopharmacol
2005;15:143-151
Dopamine Receptor D3 Genotype, Saliva
Clinical Information: The neurotransmitter dopamine acts via dopamine receptors in the central
nervous system. Dopamine receptor subtypes D1 through 5 (DRD1-5) are of interest in schizophrenia
research because many of the antipsychotic drugs interact with and block 1 or several of these receptors.
There has been a strong association between DRD2 receptor blockade and antipsychotic drug dose for
typical antipsychotics (eg, haloperidol, chlorpromazine). However, this association has not been
maintained for the atypical antipsychotics (eg, clozapine, risperidone). The atypical antipsychotic
medications have high binding affinity for the polymorphic DRD3 receptor. For DRD3, a single
nucleotide change (DRD3 25A->G) results in an amino acid coding polymorphism, Ser9Gly, which is
associated with variable response to treatment with atypical antipsychotic medications and predisposition
to tardive dyskinesia, a side effect of certain antipsychotic drugs. Worldwide, the frequency of the A
(DRD3 25A) and G (DRD3 25G) alleles is nearly equal. However, the allele frequencies are markedly
different in different populations (see below) and this may impact the risk of tardive dyskinesia within a
given population or cohort following treatment with antipsychotic drugs. Population Frequencies for
DRD3 25A and DRD3 25G Alleles: -Allele frequency - European: G=35%, A=65% - African American:
G=70%, A=30% - Han Chinese Beijing: G=37%, A=63% - Japanese: G=24%, A=76% Other
polymorphisms in the 5' promoter region of DRD3 have also been studied, but results are too preliminary
to be used in the management or diagnoses of psychiatric illnesses. Tardive dyskinesia: The DRD3 25G
polymorphism is associated with the presence and severity of typical neuroleptic-induced tardive
dyskinesia in schizophrenic patients. Higher mean movement scores were found in patients homozygous
for the DRD3 25G allele as compared to both heterozygous and DRD3 25A homozygous patients.(1,2)
The risk for tardive dyskinesia increases with the number of DRD3 25G alleles. Individuals homozygous
for the DRD3 25G allele have an odds ratio of 2.8 for developing tardive dyskinesia compared to
individuals homozygous for the DRD3 25A allele.(2) Treatment responses: The DRD3 25G allele has
been associated with treatment response to clozapine(3) and olanzapine. Among a group of Chinese
patients with schizophrenia treated with risperidone, patients homozygous for the DRD3 25A allele had a
better response, as measured by improved scores on the Positive and Negative Symptom Scale (PANSS),
a questionnaire used to evaluate symptoms associated with schizophrenia, compared to patients
homozygous for the DRD3 25G allele.(4) These improved responses included decreased social and
emotional withdrawal, improved abstract thinking, and increased spontaneity and flow of conversation. A
better response was observed in the heterozygous state (DRD3 25AG) compared to the homozygous
groups (DRD3 25GG, P=0.05; DRD3 25AA P=0.06) in another study of patients receiving a variety of
typical and atypical antipsychotics.(5)
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