03. CYP2D6 Pharmacogenomics: From Genotype to Phenotype

Let’s take a closer look at one of these enzymes. It’s the P450 2D6 enzyme…

And I’ll show you a chart here that describes some of the common alleles of these enzymes, the functional status, activity level and allele frequency. So, this chart is for Caucasians, Europeans and Northern Americans. And the way this is named is that *1 is considered the normal type allele. So, for the *1, that means the enzyme results in normal activity. So, the activity level is assigned a 1. And then the allele frequency in Caucasians in turns out is 39%. Now, when they looked at all of these 2D6 alleles, then they noticed that some people have an allele that looks a little different from the *1. So, they called this the *2 and then they figured out what exactly is different about them. And they realized that *2 is also a normal activity. So that gets assigned a normal activity. And then they find out okay, maybe 28% of Caucasians have this. Then they kept looking. So it turns out that *3, a little different configuration, has no activity. So functional status is considered to be none. The activity level is zero. And it turns out it’s pretty rare. The allele frequency is only 1.3% and so on. So *4 is no activity. The *5, no activity. The *9, *10, *41, they realized it’s decreased activity, so they give it an activity level of 0.5. And then on the opposite end of the spectrum, there are duplications. So if you can imagine an allele being duplicated, that means this allele is going to have increased activity. And indeed, there are people who actually have duplication, three or four times of this allele. So then their activity level is much higher than that of normal. And that’s also relatively rare in Caucasians.