If genetic differences between racial demographics are so small why does testing for clinical drugs need so many representative samples?

Question

Seems like a contradiction to me. If we are saying the majority of humans are incredibly genetically similar except for some genes that code for pigmentation but also there are reduced clinical efficacy for drugs based on certain races. I can understand outliers like sickle cell anemia but this diversity of sampling is required for every drug.

When they do clinical testing, pharma companies try to pull from different racial groups to ensure their drug works across demographics. If we were that genetically similar then wouldn’t pulling from one group primarily do the job?

Please don’t make this a white supermacist thing. I don’t believe in that stuff. Legitimately just curious.

In: 2

Answer 1

Because drug metabolism is one of the few things in life that really can hinge on one or two genes. It’s still usually irrelevant (e.g. race-based Tylenol dosing guidelines would look something like “who gives a shit what color you are, take some if it helps but no more than 3 grams daily) but there’s just enough potential risk that it’s worth looking into. Certain minor genetic variants that wouldn’t matter otherwise can really affect medication, and are concentrated in certain populations. Drawing from multiple racial groups can be a fair enough proxy for a genetically diverse sample, although you have to be thoughtful about what the groups actually represent.

For instance, carbamazepine is an anticonvulsant with a very finicky metabolism and potential to cause a serious rash if your immune system takes a dislike to it. A certain variant of one of the things our white blood cells use to figure out friend vs. foe leads to a much higher rash risk, and it happens to be much more common in people whose recent ancestors are from east Asia.

Sometimes it’s as simple as dosing. A colleague once told us about needing to alter the typical amount and frequency of TB medication when working on a Navajo reservation, as many of the locals metabolized the drug in question much more quickly than the average European. Again, this isn’t something that would otherwise matter in life, but affects whether it’s dosed once a day or twice a day.