The unique complexity of the CYP3A4 upstream region suggests a nongenetic explanation of its expression variability.

ObjectiveThe individually variable and unpredictable expression of CYP3A4 compromises therapies with 50% of contemporary drugs. Gene variants explain only a fraction of this variability.MethodsWe investigated the evolution of CYP3A4 transcriptional regulation by nuclear receptors such as the xenobio