Test Catalog

Interpretive Handbook

Test 60338 :
Serotonin Receptor Genotype (HTR2A and HTR2C), Saliva

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Treatment with specific antidepressant and antipsychotic medications is often guided empirically. Despite the wide array of drugs available for treatment, some patients do not initially respond to treatment, and others who respond early may eventually relapse or develop serious side effects. Antidepressant selection may be more effectively guided by genotyping polymorphic genes encoding several cytochrome P450 enzymes, the serotonin transporter, and the serotonin (5-hydroxytryptamine) receptors HTR2A and HTR2C.(1)


Drugs that bind to the serotonin receptors have a wide range of effects including altering the activation of the receptors, rendering them more or less sensitive to drug concentration, or blocking the receptor. Variations (polymorphisms) in the genes that encode for the serotonin receptor have been associated with different types of drug responses including:

-Allelic variation in the HTR2A gene has been reported to affect response to selective serotonin reuptake inhibitors (SSRI) and risk for adverse drug reactions.(2) Patients predicted to respond poorly to SSRIs due to polymorphic variants in the HTR2A/2C serotonin receptors may be considered for switching to non-SSRI antidepressants. Allelic variation in the HTR2A gene has been linked with response to the antipsychotic drugs clozapine and aripiprazole.(3)

-Treatment with antipsychotics results in significant weight gain (2-3 kg/m[2]) in some patients. Weight gain has been positively correlated with a polymorphism in the promoter of HTR2C (-759C).(4)


Allele nomenclature


Nucleotide Change

Amino Acid Change



Promoter polymorphism





IVS2+54538 A>G







Promoter polymorphism

Useful For Suggests clinical disorders or settings where the test may be helpful

Guiding treatment choice of a (selective serotonin reuptake inhibitor) SSRI or non-SSRI antidepressant


Guiding treatment choice in individuals who have a drug-metabolizer phenotype discordant with CYP450 genotypes


Identifying patients who may benefit from treatment with the antipsychotic drug clozapine and aripiprazole


Identifying those patients at risk of excessive weight gain when receiving antipsychotic medications


Genotyping patients who prefer not to have venipuncture done

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Note that in patients who have received heterologous blood transfusions before a saliva sample was acquired, the saliva samples may contain donor DNA. Return to recipient genotype usually occurs after 6 weeks. Similarly, saliva samples obtained from patients after allogeneic blood or marrow transplantation can contain donor DNA. In both cases, this may result in genotyping results that reflect the genotype of the recipient, the donor, or a blend of the donor and recipient. Results obtained under these circumstances may not accurately reflect the recipient's genotype.


Drug-drug interactions must be considered when dealing with heterozygous individuals.


This test does not detect polymorphisms other than those listed above. Other polymorphisms in the primer binding regions can affect the testing and, ultimately, the genotyping assessments made.


Direct DNA testing will not detect all genetic variants that alter protein function. Absence of a detectable gene mutation or polymorphism does not rule out the possibility that a patient has a genetic variant that may be impacting drug response or side effects.


The HTR2A gene is located on the long arm of chromosome 13 (13q). For patients with known hematologic disorders that involve deletion of 13q, call the laboratory for instructions.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Malhotra AK, Murphy GM Jr, Kennedy JL: Pharmacogenetics of psychotropic drug response. Am J Psychiatry 2004;161(5):780-796

2. Murphy GM Jr, Kremer C, Rodrigues HE, et al: Pharmacogenetics of antidepressants medication intolerance. Am J Psychiatry 2003;160(10):1830-1835

3. Arranz MJ, Murno J, Birkett J, et al: Pharmacogenetic prediction of clozapine response. Lancet 2000;355(9215):1615-1616

4. Reynolds GP, Zhang ZJ, Zhang XB: Polymorphism of the promoter region of the serotonin 5-HT2C receptor gene and clozapine-induced weight gain. Am J Psychiatry 2003;160:677-679

5. Segman RH, Heresco-Levy U, Finkel B, et al: Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry 2001;6(2):225-229

6. Segman RH, Heresco-Levy U, Finkel B, et al: Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2Cser and DRD3gly alleles to susceptibility. Psychopharmacology 2000;152(4):408-413

7. Choi MJ, Kang RH, Ham BJ, et al: Serotonin receptor 2A gene polymorphism (-1438A->G) and short-term treatment response to citalopram. Neuropsychobiology 2005;52:155-162

8. McMahon FJ, Buervenich S, Charney D, et al: Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet 2006;78:804-814

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