When you take your drugs might matter as much as what you’re taking

Circadian clock genes help align our bodies with our planet’s 24 hour light-dark cycle. Misalignment of circadian rhythms has been implicated in obesity, diabetes, and neurodegenerative disease. Yet these core clock genes are not the only ones whose expression cycles with time; new work done at the University of Pennsylvania shows that the expression of 43% of protein coding genes in mice, and a similar proportion of the noncoding DNA that is conserved between mice and men, oscillates in a similar manner. The nonconserved and noncoding DNA did not have nearly as high percentage of sequences whose transcription varied with time.

The researchers monitored expression of all genes in twelve different organs, taking samples every two hours for forty eight hours. They found that most of the oscillations were organ specific, with the liver having the most oscillating genes and the brain having the least. Only ten genes oscillated in all twelve organs, and seven of these are the core clock genes that set up the circadian rhythm for the whole body. These genes oscillated in synchrony across all of the organs.

In most of the organs, gene transcription peaked just before dawn and again just before dusk. Organs that were developmentally related shared genes that oscillated in synchrony; yet over a thousand genes were expressed in different phases in different organs. A hundred and thirty one genes were expressed in completely opposite phases in different organs.

There was a very large overlap between these newly identified circadian genes, genes known to be associated with disease, and drug targets. Fifty-six of the top one hundred best selling drugs in the united States – including Tamiflu, Ritalin, Viagra, Lunesta, and Prilosec – target the product of a circadian gene. Many of these drugs have half-lives that are less than six hours, so taking them at the proper time – when their target is actually produced in the appropriate organ – could affect their efficacy, and maybe even their dosage.

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