5 Dec, 16 | by BMJ
NEJM 1 Dec 2016 Vol 375
Can genes prove how drugs work?
Medicine is the application of neat science to a messy world. We love it when it works simply: for example, when a single gene controls a single biochemical process, which we can then block with a single chemical. Statins are often cited as an example: they block 3-hydroxy-3-methylglutaryl–coenzyme A reductase, an enzyme that is governed by the HMGCR gene. By doing so, they reduce circulating levels of low density lipoprotein cholesterol (LDL-C) and, bingo, down goes your cardiovascular risk. But for less obvious reasons, they also raise blood glucose slightly and cause muscle symptoms in many people. If your glucose is highish to start with, they may cause you to “get diabetes,” i.e. cross an artificial threshold and bundle you together with millions of different people with this scary label. But can all this really be put down to the HMGCR gene? Here’s a population study, which concludes that it can, provided you throw in a second gene locus governing LDL-C levels. more…