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Test ID: DRD4O Dopamine Receptor D4 Genotype (DRD4), Saliva

Reporting Name

DRD4 Genotype, Saliva

Useful For

Influencing the target dose of methylphenidate treatment for patients with attention deficit/hyperactivity disorder


Determining possible cause for poor response to methylphenidate in treated patients with attention deficit/hyperactivity disorder


Genotyping patients who prefer not to have venipuncture done

Specimen Type


Specimen Required

Multiple saliva genotype tests can be performed on a single specimen after a single extraction. See Multiple Saliva Genotype Tests in Special Instructions for a list of tests that can be ordered together.


Supplies: DNA Saliva Collection Kit (T651)

Container/Tube: Oragene DNA Self-Collection Kit (T651: fees apply)

Specimen Volume: Full tube

Collection Instructions:

1. Fill tube to line.

2. Send specimen in original container per kit instructions.

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Saliva Ambient

Reference Values

An interpretive report will be provided.

Day(s) and Time(s) Performed

Friday; 8 a.m.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
DRD4O DRD4 Genotype, Saliva In Process


Result ID Test Result Name Result LOINC Value
32982 48 BP Repeat Genotype 82939-0
32983 Reviewed by 18771-6
32984 Interpretation 69047-9

Clinical Information

The dopamine receptor D4 gene (DRD4) is located near the telomeric region of chromosome 11q and is a highly variable gene. A 48-base pair (bp) variable number tandem repeat (VNTR) polymorphism in exon 3 of DRD4, which ranges from 2 to 11 repeats, creates a 32- to 176-amino acid variation in the third intracellular loop on the dopamine receptor. The frequency of these alleles is shown in Table 1. The DRD4 7-repeat allele (7R) has functional consequences and is associated with lower affinity for dopamine receptor agonists and reduced signal transduction (eg, cAMP levels) compared to the more common DRD4 4-repeat allele (4R). The effect of other copy number repeats is not as well defined to date, however, and VNTRs with 6 or fewer repeats are grouped as 4R and those with 7 or more repeats as 7R.


Frequency of alleles with various DRD4 exon 3 48-bp repeats:

Allele/Number of Repeats (R)

Allelic Frequency (%)






















The DRD4 protein is expressed in a number of brain regions, with higher levels of expression in the prefrontal cortex, where animal models suggest that it inhibits neuronal firing.


Attention Deficit/Hyperactivity Disorder (ADHD):

Several studies have found associations between the DRD4 7R allele and ADHD.(1,2) Similarly, a long form (240-bp variant) of a DRD4 promotor repeat polymorphism is associated with ADHD susceptibility, possibly due to linkage disequilibrium with the DRD4 7R allele.(3)



Several studies demonstrate that the presence of the DRD4 7R allele, alone or in combination with the SLC6A4 long/long promotor polymorphism of the serotonin transporter, is associated with lower responsiveness of ADHD to methylphenidate (eg, Ritalin, Concerta), the main treatment for ADHD.(4) Methylphenidate dosage may have to be increased to effectively treat individuals with the DRD4 7R allele. Attempts to find an association between DRD4 genotype and the variability of response to antipsychotic drugs, especially clozapine, have been largely unsuccessful or have yielded conflicting results. A recent meta-analysis found that children with a 4R/4R genotype had a 66% greater chance of responding to methylphenidate than those with other genotypes. Nonsignificant results were obtained when comparing the 7R variant to other genotypes.(5)


An interpretive report will be provided.

Clinical Reference

1. Ding Y, Chi HC, Grady D, et al: Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc Natl Acad Sci U S A 2002;99(1):309-314

2. Online Inheritance in Man. National Center for Biotechnology Information, U.S. National Library of Medicine. Accessed July 2018 at

3. Kustanovich V, Ishii J, Crawford L, et al: Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 2004;9(7):711-717

4. Hamarman S, Fossella J, Ulger C, et al: Dopamine receptor 4 (DRD4) 7-repeat allele predicts methylphenidate dose response in children with attention deficit hyperactivity disorder: a pharmacogenetic study. J Child Adolesc Psychopharmacol 2004;14(4):564-574

5. Myer NM, Boland JR, and Faraone SV: Pharmacogenetics Predictors of Methylphenidate Efficacy in Childhood ADHD. Mol Psychiatry 2017, doi: 10.1038/mp.2017.234

Analytic Time

1 day

Method Name

Polymerase Chain Reaction (PCR) Followed by Sizing Analysis


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send a Pharmacogenomics Test Request (T797) with the specimen.

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: