ADRA2A Genotyping

Adrenoceptor Alpha 2A (ADRA2A) is a gene that encodes for receptors that are widely distributed within the central nervous system and periphery. Studies have shown ADRA2A variations to be associated with the effectiveness of methylphenidate (Ritalin®), a medication used to treat symptoms of attention deficit hyperactivity disorder (ADHD) [37]. The most well-studied variant of the ADRA2A gene has been found to be present in nearly 25% of the Caucasian population.

Adrenoceptors play a critical role in regulating neurotransmitter release from sympathetic nerves and from neurons that release the hormone and neurotransmitter norepinephrine in the central nervous system. ADRA2A is localized on sympathetic nerves in the brainstem, midbrain, hypothalamus, hippocampus, spinal cord, cerebral cortex, cerebellum, and septum.

Although the mechanism of action for methylphenidate in ADHD is not fully understood, one purposed mechanism is increased norepinephrine tone in the prefrontal cortex by binding to the ADRA2A receptor. The genetic variation to this receptor may contribute to methylphenidate (Ritalin®) and dexmethylphenidate (Focalin®) response. Genetic variant tested is c.-1252G>C (rs1800544).

Indications for ADRA2A Testing

Patients with ADHD that are on or are considering starting methylphenidate or dexmethylphenidate may be candidates for ADRA2A testing. Generally, assessment of medical necessity for testing is up to the provider’s clinical judgment.