Clinical Pharmacogenetics of the Major Adenosine Triphosphate−Binding Cassette and Solute Carrier Drug Transporters

Abstract

Interindividual variability in drug response is a significant problem in clinical practice, and it is likely that genetic variation among the drug transport genes are major contributors to such variability. Numerous genetic alterations affecting the members of the adenosine triphosphate-binding cassette (ABC) and solute carrier (SLC) families of transporters have been identified. Considerable data exist regarding how mutations in the ABCB1 gene that encodes p-glycoprotein impact drug disposition and response in vivo, but many study reports are conflicting on both the direction of any effect as well as the significance of any alteration. Many possible reasons for such discrepant study results have been identified, and efforts to improve the quality of such pharmacogenetic clinical association studies are ongoing. For most other clinically important transporters relatively, little clinical data exist regarding the significance of known genetic variants despite in vitro evidence of altered function for many of these transporters. What clinical data do exist suggest that certain mutations in ABCG2 and SLCO1B1 may be of importance clinically. Until the current uncertainties regarding the importance of genetic variants in drug transporter genes are clarified, the clinical application of existing pharmacogenetic data should be done with caution.