Researching Gene-Drug Interactions – Part I

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Let’s say you are interested in researching a gene. Or, maybe, let’s say you are interested in researching a drug.

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Or, maybe, just maybe, you want to know about a drug-gene interaction. Where do you find that data?

We have more and more data available to use every minute… which is a good thing. For a researcher, looking through this data the first time (or for the 10th time) the sheer amount of information available can be a little daunting. Initial searches for genes used to yield hundreds of results, and many of those results were incomplete records, or just plan confusing.

Things are improving. Head over to the National Center for Biotechnology Information and search for genes using the keyword “warfarin” and you will get a list of genes back that mention warfarin or have been associated with a record that mentions warfarin. Total hits as of 5 February 2016 was 58, with the top two being VKORC1 and CYP2C9, generally identified as two of the genes encoding products involved in warfarin efficacy.

There are other data sets that to date are even easier to use. Let’s try the same warfarin search on another resource: Online Mendelian Inheritance in Man (OMIM). The search here yields 35 hits, VKORC1 and CYP2C9 are again in the top four, but the first hit is COUMARIN RESISTANCE. A quick click and you are reading a well annotated description, almost a text book chapter, but with more than a hundred links to relevant information on the subject.

But where is all that drug interaction data coming from? PharmGKB provides a more in depth look at all of the gene variants that might influence the function of those genes and the drugs that they are associated with. The same warfain search brings us here, to a wealth of information. I will leave almost all of this data for later, but have a look at the material described in the Pathways segment. Here the role the warfarin plays in the associated gene products functional pathway is graphically displayed. The role that VKORC1 plays is readily apparent, and why warfarins suppression of its function can be seen to play a role in the clotting process.

These are just three sources, covering the same warfarin example. The barriers to this information continue to fall, providing more intuitive access. Perhaps by your second and third searches you will will be more focused on the information you want, rather than wondering how you got there.