In this project, investigators from diverse disciplines are conducting a series of integrated studies to elucidate the pharmacogenetics of membrane transport proteins. This class of proteins is of great pharmacological importance as it provides the target for many commonly used prescription drugs and is a major determinant of the absorption, distribution and elimination of many clinically used drugs. We seek to test the hypothesis that variations in the DNA sequence of the coding and non-coding region of the genes encoding membrane transporters underlie interindividual differences in response to such drugs. The specific aims of the project are as follows:
The specific aims of the project are as follows:
- Identify sequence variants in coding and noncoding regions of genes encoding selected membrane transport proteins.
- Through integrated computational and experimental methods in cells, model organisms and in humans, functionally characterize sequence variants in membrane transporters that play a role in drug disposition and response.
- Determine the biological relevance of genetic variants in membrane transporters to clinical drug disposition and response in ethnically diverse human populations.
- Deposit the data in the Pharmacogenetics Network Database, PharmGKB.