TABLE 16.
In vitro characterization of genetic polymorphisms in OAT1 and -3
In vitro function was assessed using prototypical substrates for OAT1 (methotrexate, ochratoxin A) and OAT3 (estrone sulfate, cimetidine). Nucleotide position was confirmed by PharmGKB (Hewett et al., 2002). OAT1 data from Bleasby et al. (2005) and Fujita et al. (2005). OAT3 data from Erdman et al. (2006).
| Nucleotide Change | Amino Acid Change | In Vitro Function | Protein Expression/Localization |
|---|---|---|---|
| SLC22A6 | OAT1 | ||
| G149A | R50H | ↔ | N.D. |
| C311T | P104L | ↔ | N.D. |
| T677C | I226T | ↔ | N.D. |
| C767T | A256V | ↔ | N.D. |
| C877T | R293W | ↔ | N.D. |
| G1361A | R454Q | ↓ | N.D. |
| SLC22A8 | OAT3 | ||
| C387A | F129L | ↔ | N.D. |
| C445A | R149S | ↓ | N.D. |
| C715T | Gln239STOP | ↓ | N.D. |
| T779G | I260R | ↓ | N.D. |
| C829T | R277W | ↓↔ | N.D. |
| T842C | V281A | ↔ | N.D. |
| A913T | I305F | ↓ | Normal |
| C929T | A310V | ↔ | N.D. |
| G1195T | A399S | ↔ | N.D. |
| G1342A | V448I | ↔ | N.D. |
↓, reduced function; ↔, no change in function; N.D. not determined.