HTR2A genetics (serotonin receptor 5-HT2A)

The HTR2A gene holds the blueprint for the serotonin receptor 5-HT2A, one of around 14 docking sites for serotonin. The gene is examined for known variants; studies focus above all on −1438G/A (rs6311) in the control region and T102C (rs6313), which are usually inherited together. Which variants were determined is stated in the report. The sample is EDTA blood; as a genetic test, written consent is required. The receptor is part of the “Depression genetics” analysis and is listed in the test catalogue as 5HTR2a. The result stays the same for life.

What the 5-HT2A receptor does in the body

When serotonin binds to the 5-HT2A receptor, the receptor activates the enzyme phospholipase C via a G protein (Gq); calcium rises inside the cell and the nerve cell becomes more excitable. The receptor is particularly dense on pyramidal cells of the cerebral cortex, especially in the frontal brain, where it is involved in perception, attention and the processing of stimuli. Outside the brain it is found on platelets, whose clumping it enhances, and on the smooth muscle of blood vessels and the gut, which it causes to contract. Psychedelic substances act via this receptor, and several medicines against psychosis block it.

What does an HTR2A variant mean for the action of serotonin?

T102C does not change the receptor protein – the exchange is “silent”. −1438G/A lies in the control region and could influence how much receptor is produced; cell and tissue studies have produced contradictory results on this. If more receptor is produced, cells respond more strongly to the same amount of serotonin; with less receptor, more weakly. Rare variants such as His452Tyr, by contrast, change the protein itself and dampened signal transmission inside the cell in laboratory studies. Both forms of −1438G/A and T102C are widespread; their frequency differs between population groups.

What can be read from the HTR2A genotype?

HTR2A has been studied most in pharmacogenetics: studies examined whether the variants are linked to response to antidepressants or to side effects. Some found differences, others did not; so far the variants have not become part of routine medicine selection. Links with mood, sleep or personality traits are also inconsistent and allow no statement for individuals. The genotype describes an inherited property of the serotonin response, not the amount of serotonin – that is shown by the neurotransmitter analyses. Together with TPH2 (production), the serotonin transporter (reuptake) and MAO-A (breakdown), a picture of the inherited make-up of the serotonin system emerges.

The interpretation is given in your report.