Science Buddies: "Ask an Expert"

I am participating in a science project designed to research the cause of drug reactions. My hypothesis is that drug reactions are the result of genetic mutations that change the amino acid sequence of target proteins and cause them to interact in unexpected ways with the prescribed drugs. Having followed the instructions on the science buddies website, I have completed my investigation and concluded that my hypothesis was indeed correct.

One of the drugs I investigated was Warfarin and in doing so I discovered that the rs1799853 mutation in the target protein let to the body's production of Cystine instead of Arginine which led to a change in the polarity of the amino acid. It lost its positive charge and this changed the drugs effect on the person it would have been given to in real life.

Is there a way to determine what patients might have such mutations before the drug is given to them so that we could avoid harming them? Are there plans to genetically map patients so that we can tell them which medications would be best for them before they are given? Currently, it appears that doctors use a trial and error approach. Interested in your opinion. Thank you so much for your help.

Quinn

Hi Quinn,

Excellent and timely topic you picked and one that Pharma companies worry about all the time because of the possibility of adverse drug effects in certain people. In fact there is a whole area of research called pharmacogenetics that studies drug interactions in relation to genetic variations.

Obviously a new drug cannot be tested on every person, but once a particular gene variant has been identified, the physician who is thinking about prescribing the drug for their patient can screen the person’s DNA to determine if that sequence is present. If it is they might want to choose a different drug, adjust the dose or use a combination of drugs to attempt to counteract the adverse effects.

This DNA screening is the basis for the recent upsurge in ‘personalized’ medicine. Here’s a good reference that reviews this subject: http://www.nature.com/scitable/topicpag ... dicine-643

So, to answer your question—yes, the sequence variant that causes a person to be sensitive to a particular drug can be identified in the same way as CSI people identify an individual as a suspect—by doing a polymerase chain reaction assay with a set of primers specific for the DNA sequence of interest. Here’s a paper that will give you some information on how this is done, but there is tons more information on the web: http://www.plosone.org/article/info:doi ... ne.0004584

If you have more questions please post to this same thread and we will try to help you.

Best wishes,

Sybee