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Interpretive Handbook

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Test 83303 :
Serotonin Receptor Genotype (HTR2A and HTR2C)

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:

-HTR2A receptor

 - The -1439A->G polymorphism is associated with SSRI response and side effects and antipsychotic response. The GG genotype responds better and has higher adverse drug reactions to SSRI than the AG or AA genotypes.(1) The GG genotype is also associated with poorer response to clozapine and typical antipsychotics.(2)

 - The 74C->A polymorphism has not been studied in vivo but in vitro studies show that the A allele causes a 30 fold decrease in aripiprazole agonist potency so individuals with the A allele are expected to respond poorly to the drug.(3)

 - The IVS2+5453A->G polymorphism is associated with citalopram response. The GG genotype responds to citalopram poorer than the AA genotype.(4)

 - For the 1354C->T polymorphism, the TT and CT genotypes are associated with poorer response to clozapine.(5)

-HTR2C receptor

 - For the -759C->T polymorphism, the CT or TT genotypes are associated with less weight gain caused by antipsychotic administration.(6-7)


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 antidepressant and antipsychotic drug selection


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


Identifying those patients receiving antipsychotic medications at risk for excessive weight gain

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

Patients who have received a heterologous blood transfusion within the preceding 6 weeks, or who have received an allogeneic blood or marrow transplant, can have inaccurate genetic test results due to presence of donor DNA. 


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


This test does not detect polymorphisms other than those listed above.


The HTR2A gene is located on the long arm of chromosome 13 (13q). Patients identified with hematologic disorders that involve deletion of 13q should 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. Kato M, Serretti A: Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Molecular Psychiatry 2010;15:473-500

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

3. Davies MA, Setola V, Strachan RT, et al: Pharmacologic analysis of non-synonymous coding h5-HT(2A) SNPs reveals alterations in atypical antipsychotic and agonist efficacies. Pharmacogenomics Journal, 2006;6:42-51

4. 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

5. Masellis M, Basile V, Meltzer HY, et al: Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology, 1998;19:123-132

6. 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

7. Templeman LA, Reynolds GP, Arranz B, San L: Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenetics and Genomics, 2005;15(4):195-200