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Interpretive Handbook

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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) resulting in increased drug levels and increased risk for adverse drug reactions.(2) Patients with polymorphic variants in the HTR2A/2C serotonin receptors may be considered for switching to non-SSRI antidepressants that block the type 2 receptors. Allelic variations in the HTR2A and HTR2C genes have been linked with response to the antipsychotic drug clozapine. The presence of the HTR2A receptor allele His452 has been reported to predict favorable response to clozapine therapy.(3)

-Treatment with atypical 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)

-Allelic variation in the HTR2A and HTR2C genes has also been associated with increased risk of tardive dyskinesia in schizophrenic patients.(5,6)

-Allelic variation in the HTR2A gene and its promoter have been associated with improved effectiveness of citalopram in major depression disorder.

Allele nomenclature

Gene

Nucleotide Change

Amino Acid Change

HTR2A

1438G->A

Promoter polymorphism

HTR2A

74C->A

Thr25Asp

HTR2A

IVS2+54538 A->G

Non-coding

HTR2A

1354C->T

His452Tyr

HTR2C

-759C->T

Promoter polymorphism

 

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

Guiding treatment choice of an (selective serotonin reuptake inhibitor) SSRI or non-SSRI antidepressant. Individuals homozygous for the IVS2+54538 A allele have improved probability of response to citalopram, in contrast to individuals homozygous or heterozygous for the IVS2 G allele. Individuals with major depression disorders are more likely to respond to citalopram if they are homozygous for the -1438G promoter allele.

 

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

 

Identifying those patients receiving atypical antipsychotic medications with excessive weight gain who may benefit by switching to different 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.

 

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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