TABLE 20.
In vitro characterization of genetic polymorphisms in MRP1–4
In vitro function was assessed using prototypical substrates for MRP1 (leukotriene C4, estradiol 17β-glucuronide, methotrexate), MRP2 (leukotriene C4, estradiol 17β-glucuronide), MRP3 (estradiol 17β-glucuronide), and MRP4 (zidovudine, adefovir). Nucleotide position was confirmed by PharmGKB (Hewett et al., 2002). MRP1 data from Conrad et al. (2001); Conrad et al. (2002); Leslie et al. (2003); LŽtourneau et al. (2005). MRP2 data from Itoda et al. (2002); Moriya et al. (2002); Hirouchi et al. (2004); Izzedine et al. (2006); Rau et al. (2006); Haenisch et al. (2007); Sai et al. (2008). MRP3 data from Lang et al. (2004); Lee et al., 2004b; Fukushima-Uesaka et al. (2007); Kobayashi et al. (2008). MRP4 data from Abla et al. (2008) and Krishnamurthy et al. (2008).
| Nucleotide Change | Amino Acid Change | In Vitro Function | Protein Expression/Localization |
|---|---|---|---|
| ABCC1 | MRP1 | ||
| G128C | C43S | ↑↔ | Intracellular |
| C218T | T73I | ↑↔ | Normal |
| C257T | S92F | ↓↔ | Normal |
| C350T | T117M | ↓↔ | Normal |
| G689A | R230Q | ↔ | Normal |
| G1057A | V353M | N.D. | N.D. |
| G1299T | R433S | ↓↔ | Normal |
| G1898A | R633Q | ↓↔ | Normal |
| G2012T | G671V | ↔ | Normal |
| G2168A | R723Q | ↓ | Normal |
| G2965A | A989T | ↓↔ | Normal |
| G3140C | C1047S | ↑↔ | Normal |
| G3173A | R1058Q | ↔ | Normal |
| C4535T | S1512L | ↔ | Normal |
| ABCC2 | MRP2 | ||
| C-24T | N.D. | N.D. | |
| G1058A | R353H | N.D. | N.D. |
| G1249A | V417I | ↔ | Normal |
| C2366T | S789F | ↑↓ | Intracellular |
| T2780G | L927R | N.D. | N.D. |
| C3298T | R1100C | N.D. | N.D. |
| G3299A | R1100H | N.D. | N.D. |
| T3563A | V1188E | N.D. | N.D. |
| G4348A | A1450T | ↔ | Normal/Intracellular |
| G4544A | C1515Y | N.D. | N.D. |
| ABCC3 | MRP3 | ||
| G32A | G11D | ↔ | Normal |
| C202T | H68Y | N.D. | N.D. |
| G296A | R99Q | N.D. | Normal |
| C1037T | S346F | ↓ | Normal |
| C1537A | Q513K | N.D. | N.D. |
| T1643A | L548Q | N.D. | N.D. |
| G1820A | S607N | ↓ | Normal |
| C2221T | Gln741STOP | N.D. | N.D. |
| G2293C | V765L | ↔ | Normal |
| G2395A | V799M | N.D. | N.D. |
| C2758T | P920S | ↑ | Normal |
| G2768A | R923Q | ↑ | Normal |
| C3657A | S1219R | N.D. | N.D. |
| C3856G | R1286G | ↔ | Normal |
| G3890A | R1297H | N.D. | N.D. |
| C4042T | R1348C | ↑ | Normal |
| A4094G | Q1365R | ↔ | Normal |
| C4141A | R1381S | ↔ | Intracellular |
| C4217T | T1406M | N.D. | N.D. |
| G4267A | G1423R | N.D. | N.D. |
| ABCC4 | MRP4 | ||
| C52A | L18I | N.D. | N.D. |
| C232G | P78A | ↓↔ | Normal |
| T551C | M184T | N.D. | N.D. |
| G559T | G187W | ↓ | Reduced |
| A877G | K293E | ↔ | Normal |
| G912T | K304N | ↔ | Normal |
| C1067T | T356M | N.D. | N.D. |
| C1208T | P403L | ↓↔ | Normal |
| G1460A | G487E | ↓ | Normal |
| A1492G | K498E | ↔ | Normal |
| A1875G | I625M | N.D. | N.D. |
| C2000T | P667L | N.D. | N.D. |
| A2230G | M744V | ↔ | Normal |
| G2269A | E757K | N.D. | Intracellular |
| G2459T | R820I | N.D. | N.D. |
| G2560T | V854F | N.D. | N.D. |
| G2698T | V900L | N.D. | N.D. |
| G2867C | C956S | ↑↔ | Normal |
| G3211A | V1071I | ↔ | Normal |
| C3425T | T1142M | N.D. | N.D. |
| G3659A | R1220Q | N.D. | N.D. |
| A3941G | Q1314R | N.D. | N.D. |
↓, reduced function; ↑, increased function; ↔, no change in function; N.D. not determined.