You mentioned that one of the most popular hits of
things that people are interested in are the Warfarin pathways.
>> Yes.
>> Now why, why is that?
>> So, Warfarin is pretty much the most advanced case of
pharmocogenetics that has been studied. Why do I say that? Warfarin has more
than one drug that impacts its response. And we actually know what
a lot of those, more than one gene. I'm sorry. Warfarin has
more than one gene that's important for understanding its response. And
we actually know what a lot of those genes are, and
how to combine the information from more than one gene. That's,
that's a frontier. There are many genes drugs for which we know
there are several genes. But, we don't know how to combine
the information yet. We do for for Warfarin, so that's the first
thing. The second thing about Warfarin is that we also know
some of the environmental variables that
effect Warfarin response. How much green
leafy vegetables you're eating? what your height and
weight is? What other drugs you're on? That all
combines to have Warfarin be the single best drug
that we have for predicting response based on the
combination of genetics and environmental factors. The other thing
that I should have actually mentioned right off the
bat is there are something between 30 and 50
million Americans alone on this drug. And probably obviously
twice that, or more Internationally. So we're talking
a hundred million people on this drug. There are
new drugs coming out that are hoping to
knock it off as the leader. bBt today Warfarin
is still an incredibly important drug worldwide and
so accurate dosing, especially for a dangerous drug like
Warfarin. As you may know, Warfarin is anti-coagulant
and it makes it harder to clot your blood.
That's good if you've had a heart attack, it's good if you've had a stroke. It's
good if you've had a clot in your lung or in your legs. But if you
have too much of it, it can kill
you with internal spontaneous hemorrhage. So there's this
very narrow range, we have to get it
right, and that's where the genetics can help.
>> Right, it sounds like blood clotting
is obviously important when we cut ourselves
and we're bleeding. But you know if it's blocking our hearts that's not so good.
>> Not so good.
>> Well you
mentioned that there are so many people on Warfarin. the variation in
the human genome that exists on the PharmGKB side for example, does it sort
of separate? Is it able to
document the pharmaco-kinetic and the pharmaco-dynamic pathways
separately? Does it combine them, how do
you how do you present that information?
>> Yeah so we, those are two separate. Good for you for
knowing about this. And, and good for your class. in the case
of Warfarin, there are both pharmaco-kinetic and pharmaco
determinants to the response. And there are genetic variations
on the pharmaco-kinetic side that change the rate at
which it's metabolized. And one of the most important
genes is called CYP2C9. there's another one called
a CYP4F2, but 2C9 to take as an example.
It's well known that if you're going to metabolize Warfarin
more slowly, you're going to need less of it. And,
and if you take the normal dose when
you're a slow metabolizer, you're going to wind up with
effectively an overdose, and too much bleeding. There on
the pharmaco-dynamic side, there's a gene, again with a
terrible name. It's called VKORC1 or Vitamin K Oxoreductase
Component one, which is actually the target. It's, it's
the, it's the protein which the drug Warfarin binds
to to inhibit clotting. And there are some variations.
Both inside this gene, but also in the control
regions of the gene. That it controls it's expression, that
markedly changes it's levels. And there are some variations that
are very important for determining Warfarin does in that. So,
it's a great story, because there's this one PD
gene that seems dominant, this one PK gene that seems
dominant. Together you can come darn close to predicting what
the right dose will be for, for an individual patient.
>> Even without
needing to see them clinically first?
>> That's right. You, it, it does, you do
best if you have their age, because there are
some age effects and gender. There's some sex effects
the genetics. and then, ethnicity. You would hope that
ethnicity would drop out, because you would hope that
once we have the genetic measurements. Who cares what
your ancestry is? But I must say that our
ability to predict those for African-descent people is still
not as good and so in our lab, we're working very hard. The hypothesis would be
that there are additional genetic variations seen in
that population that have not been studied yet.
That, with knowledge of those, we'll be able
to get our level of prediction for, African
descent people to be as good as where we are now for European and Asian descent.
>> Thank you so much for chatting with us.
>> Alright. It's my pleasure. Thanks for doing this.
>> Yeah, of course.