Eli5: what does it mean if “a patient is heterozygous for the Val158Met polymorphism in the catechol-o-methyltransferase gene. They have one copy of the Met allele and one copy of the Val allele”

Question

How would that affect how the patient reacts to medications? Especially stimulants such as adderall, Ritalin, etc.

In: Biology

Answer 1

I can answer the genetic part. One of our genes is the “recipe”, or instructions, for making catechol-O-methyltransferase, which is an enzyme that breaks down dopamine and epinephrine so their signals are temporary instead of going on and on.

The 158th amino acid in catechol-O-methyltransferase is supposed to be valine (Val) but if you have a certain mutation (basically a typo in your DNA) your body puts methionine (Met) in that position instead. The resulting mutated protein still does the job, but it works about 2/3 as well as the valine version.

In general you have two copies of every gene, one from your dad and one from your mom. Being heterozygous means your two copies are different; being “heterozygous for Val158Met” means you have one copy of the normal gene and one copy of the slightly-defective gene, and that should mean that about half your catechol-O-methyltransferase is the full-functioning stuff and the other half is the “works 2/3 as well” stuff, so overall one of your brain chemicals is running about 83% of full strength.

What this means for a person is complex and I’m not trained on that side, but according to some fast reading we usually see effects on memory, behavior and/or motor function.